The Radiosensitizing Potentials of Silymarin/Silibinin in Cancer: A Systematic Review


Cite item

Full Text

Abstract

Introduction:Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment and tumor resistance to ionizing radiation are the chief challenges of radiotherapy that can lead to different adverse effects. It was shown that the combined treatment of radiotherapy and natural bioactive compounds (such as silymarin/silibinin) can alleviate the ionizing radiation-induced adverse side effects and induce synergies between these therapeutic modalities. In the present review, the potential radiosensitization effects of silymarin/silibinin during cancer radiation exposure/radiotherapy were studied.

Methods:According to the PRISMA guideline, a systematic search was performed for the identification of relevant studies in different electronic databases of Google Scholar, PubMed, Web of Science, and Scopus up to October 2022. We screened 843 articles in accordance with a predefined set of inclusion and exclusion criteria. Seven studies were finally included in this systematic review.

Results:Compared to the control group, the cell survival/proliferation of cancer cells treated with ionizing radiation was considerably less, and silymarin/silibinin administration synergistically increased ionizing radiation-induced cytotoxicity. Furthermore, there was a decrease in the tumor volume, weight, and growth of ionizing radiation-treated mice as compared to the untreated groups, and these diminutions were predominant in those treated with radiotherapy plus silymarin/ silibinin. Furthermore, the irradiation led to a set of biochemical and histopathological changes in tumoral cells/tissues, and the ionizing radiation-induced alterations were synergized following silymarin/silibinin administration (in most cases).

Conclusion:In most cases, silymarin/silibinin administration could sensitize the cancer cells to ionizing radiation through an increase of free radical formation, induction of DNA damage, increase of apoptosis, inhibition of angiogenesis and metastasis, etc. However, suggesting the use of silymarin/silibinin during radiotherapeutic treatment of cancer patients requires further clinical studies.

About the authors

Jitendra Gupta

Institute of Pharmaceutical Research, GLA University

Email: info@benthamscience.net

Abduladheem Jalil

Medical Laboratories Techniques Department, Al-Mustaqbal University College

Author for correspondence.
Email: info@benthamscience.net

Zainab Riyad Muedii

National University of Science and Technology, Dhi Qar, Iraq, Thi Qar University

Email: info@benthamscience.net

Zafar Aminov

Department of Public Health and Healthcare Management, Samarkand State Medical Institute

Email: info@benthamscience.net

Fahad Alsaikhan

College of Pharmacy, Prince Sattam Bin Abdulaziz University

Author for correspondence.
Email: info@benthamscience.net

Andrés Ramírez-Coronel

Psychometry and Ethology Laboratory, Azogues Campus Nursing Career, Health and Behavior Research Group (HBR), Catholic University of Cuenca

Email: info@benthamscience.net

Pushpamala Ramaiah

Faculty of Nursing, Umm al-Qura University

Email: info@benthamscience.net

Bagher Farhood

Department of Medical Physics and Radiology, Faculty of Paramedical Sciences,, Kashan University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Farhood, B.; Geraily, G.; Alizadeh, A. Incidence and mortality of various cancers in Iran and compare to other countries: A review article. Iran. J. Public Health, 2018, 47(3), 309-316. PMID: 29845017
  2. Mortezaee, K.; Narmani, A.; Salehi, M.; Bagheri, H.; Farhood, B.; Haghi-Aminjan, H.; Najafi, M. Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer. Life Sci., 2021, 269, 119020. doi: 10.1016/j.lfs.2021.119020 PMID: 33450258
  3. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249. doi: 10.3322/caac.21660 PMID: 33538338
  4. Najafi, M.; Hooshangi Shayesteh, M.R.; Mortezaee, K.; Farhood, B.; Haghi-Aminjan, H. The role of melatonin on doxorubicin-induced cardiotoxicity: A systematic review. Life Sci., 2020, 241, 117173. doi: 10.1016/j.lfs.2019.117173 PMID: 31843530
  5. Talakesh, T.; Tabatabaee, N.; Atoof, F.; Aliasgharzadeh, A.; Sarvizade, M.; Farhood, B. Effect of nano-curcumin on radiotherapy-induced skin reaction in breast cancer patients: A randomized, triple-blind, placebo-controlled trial. Curr Radiopharm., 2022, 15(4), 332-340.
  6. Mortezaee, K.; Parwaie, W.; Motevaseli, E.; Mirtavoos-Mahyari, H.; Musa, A.E.; Shabeeb, D.; Esmaely, F.; Najafi, M.; Farhood, B. Targets for improving tumor response to radiotherapy. Int. Immunopharmacol., 2019, 76, 105847. doi: 10.1016/j.intimp.2019.105847 PMID: 31466051
  7. Ford, E.C.; Terezakis, S. How safe is safe? Risk in radiotherapy. Int. J. Radiat. Oncol. Biol. Phys., 2010, 78(2), 321-322. doi: 10.1016/j.ijrobp.2010.04.047 PMID: 20832662
  8. Baskar, R.; Lee, K.A.; Yeo, R.; Yeoh, K.W. Cancer and radiation therapy: current advances and future directions. Int. J. Med. Sci., 2012, 9(3), 193-199. doi: 10.7150/ijms.3635 PMID: 22408567
  9. Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Shabeeb, D.; Musa, A.E. Resveratrol as an adjuvant for normal tissues protection and tumor sensitization. Curr. Cancer Drug Targets, 2020, 20(2), 130-145. doi: 10.2174/1568009619666191019143539 PMID: 31738153
  10. Farhood, B.; Geraily, G.; Abtahi, S.M.M. A systematic review of clinical applications of polymer gel dosimeters in radiotherapy. Appl. Radiat. Isot., 2019, 143, 47-59. doi: 10.1016/j.apradiso.2018.08.018 PMID: 30390500
  11. Bagheri, H.; Rabie Mahdavi, S.; Shekarchi, B.; Manouchehri, F.; Farhood, B. Measurement of the contralateral breast photon and thermal neutron doses in breast cancer radiotherapy: A comparison between physical and dynamic wedges. Radiat. Prot. Dosimetry, 2018, 178(1), 73-81. doi: 10.1093/rpd/ncx076 PMID: 28591863
  12. Moding, E.J.; Kastan, M.B.; Kirsch, D.G. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat. Rev. Drug Discov., 2013, 12(7), 526-542. doi: 10.1038/nrd4003 PMID: 23812271
  13. Mortezaee, K.; Salehi, E.; Mirtavoos-mahyari, H.; Motevaseli, E.; Najafi, M.; Farhood, B.; Rosengren, R.J.; Sahebkar, A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol., 2019, 234(8), 12537-12550. doi: 10.1002/jcp.28122 PMID: 30623450
  14. Liauw, S.L.; Connell, P.P.; Weichselbaum, R.R. New paradigms and future challenges in radiation oncology: An update of biological targets and technology. Sci. Transl. Med., 2013, 5(173), 173sr2. doi: 10.1126/scitranslmed.3005148 PMID: 23427246
  15. Farhood, B.; Goradel, N.H.; Mortezaee, K.; Khanlarkhani, N.; Salehi, E.; Nashtaei, M.S.; Mirtavoos-mahyari, H.; Motevaseli, E.; Shabeeb, D.; Musa, A.E.; Najafi, M. Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clin. Transl. Oncol., 2019, 21(3), 268-279. doi: 10.1007/s12094-018-1934-0 PMID: 30136132
  16. Mortezaee, K.; Shabeeb, D.; Musa, A.E.; Najafi, M.; Farhood, B. Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr. Clin. Pharmacol., 2019, 14(1), 41-53. doi: 10.2174/1574884713666181025141559 PMID: 30360725
  17. Narmani, A.; Farhood, B.; Haghi-Aminjan, H.; Mortezazadeh, T.; Aliasgharzadeh, A.; Mohseni, M.; Najafi, M.; Abbasi, H. Gadolinium nanoparticles as diagnostic and therapeutic agents: Their delivery systems in magnetic resonance imaging and neutron capture therapy. J. Drug Deliv. Sci. Technol., 2018, 44, 457-466. doi: 10.1016/j.jddst.2018.01.011
  18. Alireza, G.; Bagher, F.; Farshid, A.N. Histopathological evaluation of nanocurcumin for mitigation of radiation-induced small intestine injury. Curr Radiopharm., 2022, 16(1), 57-63.
  19. Najafi, M.; Taeb, S.; Farhood, B.; Amini, P.; Nodooshan, S.J.; Ashrafizadeh, M.; Aliasgharzadeh, A.; Vakili, Z.; Tavakoli, S.; Aryafar, T.; Musa, A.E. Imperatorin attenuates the proliferation of MCF-7 cells in combination with radiotherapy or hyperthermia. Curr. Radiopharm., 2022, 15(3), 236-241. doi: 10.2174/1874471015666220318122202 PMID: 35306999
  20. Nodooshan, S.J.; Amini, P.; Ashrafizadeh, M.; Tavakoli, S.; Aryafar, T.; Khalafi, L.; Musa, A.E.; Mahdavi, S.R.; Najafi, M.; Ahmadi, A.; Farhood, B. Suberosin attenuates the proliferation of MCF-7 breast cancer cells in combination with radiotherapy or hyperthermia. Curr. Drug Res. Rev., 2021, 13(2), 148-153. doi: 10.2174/2589977512666201228104528 PMID: 33371865
  21. Farhood, B.; Hassanzadeh, G.; Amini, P.; Shabeeb, D.; Musa, A.E.; Khodamoradi, E.; Mohseni, M.; Aliasgharzadeh, A.; Moradi, H.; Najafi, M. Mitigation of radiation-induced gastrointestinal system injury using resveratrol or alpha-lipoic acid: A pilot histopathological study. Antiinflamm. Antiallergy Agents Med. Chem., 2020, 19(4), 413-424. doi: 10.2174/1871523018666191111124028 PMID: 31713500
  22. Motallebzadeh, E.; Tameh, A.A.; Zavareh, S.A.T.; Farhood, B.; Aliasgharzedeh, A.; Mohseni, M. Neuroprotective effect of melatonin on radiation-induced oxidative stress and apoptosis in the brainstem of rats. J. Cell. Physiol., 2020, 235(11), 8791-8798. doi: 10.1002/jcp.29722 PMID: 32324264
  23. Yahyapour, R.; Amini, P.; Saffar, H.; Motevaseli, E.; Farhood, B.; Pooladvand, V.; Shabeeb, D.; Musa, A.E.; Najafi, M. Protective effect of metformin, resveratrol and alpha-lipoic acid on radiation- induced pneumonitis and fibrosis: A histopathological study. Curr. Drug Res. Rev., 2019, 11(2), 111-117. doi: 10.2174/2589977511666191018180758 PMID: 31875783
  24. Khezerloo, D.; Mortezazadeh, T.; Farhood, B.; Sheikhzadeh, P.; Seyfizadeh, N.; Pezhman, L. The effect of date palm seed extract as a new potential radioprotector in gamma-irradiated mice. J. Cancer Res. Ther., 2019, 15(3), 517-521. doi: 10.4103/jcrt.JCRT_1341_16 PMID: 31169213
  25. Aliasgharzadeh, A.; Farhood, B.; Amini, P.; Saffar, H.; Motevaseli, E.; Rezapoor, S.; Nouruzi, F.; Shabeeb, D.H.; Eleojo Musa, A.; Mohseni, M.; Moradi, H.; Najafi, M. Melatonin attenuates upregulation of Duox1 and Duox2 and protects against lung injury following chest irradiation in rats. Cell J., 2019, 21(3), 236-242. PMID: 31210428
  26. Azmoonfar, R.; Amini, P.; Saffar, H.; Rezapoor, S.; Motevaseli, E.; Cheki, M.; Yahyapour, R.; farhood, B.; Nouruzi, F.; Khodamoradi, E.; Shabeeb, D.; Eleojo Musa, A.; Najafi, M. Metformin protects against radiation-induced pneumonitis and fibrosis and attenuates upregulation of dual oxidase genes expression. Adv. Pharm. Bull., 2018, 8(4), 697-704. doi: 10.15171/apb.2018.078 PMID: 30607342
  27. Farhood, B.; Aliasgharzadeh, A.; Amini, P.; Saffar, H.; Motevaseli, E.; Rezapoor, S.; Nouruzi, F.; Shabeeb, D.; Eleojo Musa, A.; Ashabi, G.; Mohseni, M.; Moradi, H.; Najafi, M. Radiation-induced dual oxidase upregulation in rat heart tissues: Protective effect of melatonin. Medicina, 2019, 55(7), 317. doi: 10.3390/medicina55070317 PMID: 31252673
  28. Najafi, M.; Motevaseli, E.; Shirazi, A.; Geraily, G.; Rezaeyan, A.; Norouzi, F.; Rezapoor, S.; Abdollahi, H. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications. Int. J. Radiat. Biol., 2018, 94(4), 335-356. doi: 10.1080/09553002.2018.1440092 PMID: 29504497
  29. Allison, R.; Dicker, A. Minimizing morbidity in radiation oncology: a special issue from future oncology. Future Oncol., 2014, 10(15), 2303-2305. doi: 10.2217/fon.14.195 PMID: 25525839
  30. Arabzadeh, A.; Mortezazadeh, T.; Aryafar, T.; Gharepapagh, E.; Majdaeen, M.; Farhood, B. Therapeutic potentials of resveratrol in combination with radiotherapy and chemotherapy during glioblastoma treatment: A mechanistic review. Cancer Cell Int., 2021, 21(1), 391. doi: 10.1186/s12935-021-02099-0 PMID: 34289841
  31. Sheikholeslami, S.; Khodaverdian, S.; Dorri-Giv, M.; Mohammad Hosseini, S.; Souri, S.; Abedi-Firouzjah, R.; Zamani, H.; Dastranj, L.; Farhood, B. The radioprotective effects of alpha-lipoic acid on radiotherapy-induced toxicities: A systematic review. Int. Immunopharmacol., 2021, 96, 107741. doi: 10.1016/j.intimp.2021.107741 PMID: 33989970
  32. Amini, P.; Nodooshan, S.J.; Ashrafizadeh, M.; Eftekhari, S-M.; Aryafar, T.; Khalafi, L.; Musa, A.E.; Mahdavi, S.R.; Najafi, M.; Farhood, B. Resveratrol induces apoptosis and attenuates proliferation of MCF-7 cells in combination with radiation and hyperthermia. Curr. Mol. Med., 2021, 21(2), 142-150. doi: 10.2174/18755666MTA2pODE0z PMID: 32436827
  33. Ahmed, R.F.; Moussa, R.A.; Eldemerdash, R.S.; Zakaria, M.M.; Abdel-Gaber, S.A. Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway. Iran. J. Basic Med. Sci., 2019, 22(12), 1483-1492. PMID: 32133068
  34. Comelli, M.C.; Mengs, U.; Schneider, C.; Prosdocimi, M. Toward the definition of the mechanism of action of silymarin: Activities related to cellular protection from toxic damage induced by chemotherapy. Integr. Cancer Ther., 2007, 6(2), 120-129. doi: 10.1177/1534735407302349 PMID: 17548791
  35. de Oliveira, D.R.; Tintino, S.R.; Braga, M.F.; Boligon, A.A.; Athayde, M.L.; Coutinho, H.D.; de Menezes, I.R.; Fachinetto, R. In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin. BioMed Res. Int., 2015, 2015, 292797. PMID: 25866771
  36. Ferenci, P. Silymarin in the treatment of liver diseases: What is the clinical evidence? Clin. Liver Dis., 2016, 7(1), 8-10. doi: 10.1002/cld.522 PMID: 31041017
  37. Ferenci, P.; Dragosics, B.; Dittrich, H.; Frank, H.; Benda, L.; Lochs, H.; Meryn, S.; Base, W.; Schneider, B. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol., 1989, 9(1), 105-113. doi: 10.1016/0168-8278(89)90083-4 PMID: 2671116
  38. Abenavoli, L.; Milic, N. Silymarin for liver disease. In: Liver Pathophysiology; Muriel, P., Ed.; Academic Press: Boston, 2017; pp. 621-631. doi: 10.1016/B978-0-12-804274-8.00045-X
  39. Gazák, R.; Walterová, D.; Kren, V. Silybin and silymarin--new and emerging applications in medicine. Curr. Med. Chem., 2007, 14(3), 315-338. doi: 10.2174/092986707779941159 PMID: 17305535
  40. Testino, G.; Leone, S.; Ansaldi, F.; Borro, P. Silymarin and S-adenosyl-L-methionine (SAMe): Two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view. Minerva Gastroenterol. Dietol., 2013, 59(4), 341-356. PMID: 24212353
  41. Zholobenko, A.; Modriansky, M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia, 2014, 97, 122-132. doi: 10.1016/j.fitote.2014.05.016 PMID: 24879900
  42. Vargas-Mendoza, N.; Madrigal-Santillán, E.; Morales-González, A.; Esquivel-Soto, J.; Esquivel-Chirino, C.; García-Luna Y González-Rubio, M.; Gayosso-de-Lucio, J.A.; Morales-González, J.A. Hepatoprotective effect of silymarin. World J. Hepatol., 2014, 6(3), 144-149. doi: 10.4254/wjh.v6.i3.144 PMID: 24672644
  43. Surai, P. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants, 2015, 4(1), 204-247. doi: 10.3390/antiox4010204 PMID: 26785346
  44. Guzel, S.; Sahinogullari, Z.U.; Canacankatan, N.; Antmen, S.E.; Kibar, D.; Coskun Yilmaz, B. Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats. Drug Chem. Toxicol., 2020, 43(6), 630-636. doi: 10.1080/01480545.2019.1584208 PMID: 30862206
  45. Zhu, Z.; Sun, G. Silymarin mitigates lung impairments in a rat model of acute respiratory distress syndrome. Inflammopharmacology, 2018, 26(3), 747-754. doi: 10.1007/s10787-017-0407-3 PMID: 29098546
  46. Singh, M.; Kadhim, M.M.; Turki Jalil, A.; Oudah, S.K.; Aminov, Z.; Alsaikhan, F.; Jawhar, Z.H.; Ramírez-Coronel, A.A.; Farhood, B. A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity. Cancer Cell Int., 2023, 23(1), 88. doi: 10.1186/s12935-023-02936-4 PMID: 37165384
  47. Taleb, A; Ahmad, KA; Ihsan, AU; Qu, J; Lin, N; Hezam, K Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomed. Pharmacother., 2018, 102, 689-698. doi: 10.1016/j.biopha.2018.03.140
  48. Ferraz, A.C.; Almeida, L.T.; da Silva Caetano, C.C.; da Silva Menegatto, M.B.; Souza Lima, R.L.; de Senna, J.P.N.; de Oliveira Cardoso, J.M.; Perucci, L.O.; Talvani, A.; Geraldo de Lima, W.; de Mello Silva, B.; Barbosa Reis, A.; de Magalhães, J.C.; Lopes de Brito Magalhães, C. Hepatoprotective, antioxidant, anti-inflammatory, and antiviral activities of silymarin against mayaro virus infection. Antiviral Res., 2021, 194, 105168. doi: 10.1016/j.antiviral.2021.105168 PMID: 34437912
  49. Post-White, J.; Ladas, E.J.; Kelly, K.M. Advances in the use of milk thistle (Silybum marianum). Integr. Cancer Ther., 2007, 6(2), 104-109. doi: 10.1177/1534735407301632 PMID: 17548789
  50. Hosseinabadi, T.; Lorigooini, Z.; Tabarzad, M.; Salehi, B.; Rodrigues, C.F.; Martins, N.; Sharifi-Rad, J. Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer. Phytother. Res., 2019, 33(11), 2849-2861. doi: 10.1002/ptr.6470 PMID: 31407422
  51. Abd Eldaim, M.A.; Barakat, E.R.; Alkafafy, M.; Elaziz, S.A.A. Antioxidant and anti-apoptotic prophylactic effect of silymarin against lead-induced hepatorenal toxicity in rats. Environ. Sci. Pollut. Res. Int., 2021, 28(41), 57997-58006. doi: 10.1007/s11356-021-14722-8 PMID: 34100211
  52. Barros, T.M.B.; Lima, A.P.B.; Almeida, T.C.; da Silva, G.N. Inhibition of urinary bladder cancer cell proliferation by silibinin. Environ. Mol. Mutagen., 2020, 61(4), 445-455. doi: 10.1002/em.22363 PMID: 32078183
  53. Yu, H.C.; Chen, L.J.; Cheng, K.C.; Li, Y.X.; Yeh, C.H.; Cheng, J.T. Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog. Phytother. Res., 2012, 26(5), 709-715. doi: 10.1002/ptr.3618 PMID: 22016029
  54. Wu, T.; Liu, W.; Guo, W.; Zhu, X. Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells. Biomed. Pharmacother., 2016, 81, 460-467. doi: 10.1016/j.biopha.2016.04.039 PMID: 27261626
  55. Kim, S.H.; Choo, G.S.; Yoo, E.S.; Woo, J.S.; Lee, J.H.; Han, S.H.; Jung, S.H.; Kim, H.J.; Jung, J.Y. Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis. Oncol. Lett., 2021, 21(6), 492. doi: 10.3892/ol.2021.12753 PMID: 33968208
  56. Féher, J.; Lengyel, G. Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr. Pharm. Biotechnol., 2012, 13(1), 210-217. doi: 10.2174/138920112798868818 PMID: 21466434
  57. Koltai, T.; Fliegel, L. Role of silymarin in cancer treatment: Facts, hypotheses, and questions. J. Evid. Based Integr. Med., 2022, 27, 2515690x211068826.
  58. Singh, R.P.; Agarwal, R. Flavonoid antioxidant silymarin and skin cancer. Antioxid. Redox Signal., 2002, 4(4), 655-663. doi: 10.1089/15230860260220166 PMID: 12230878
  59. Zhu, W.; Zhang, J.S.; Young, C.Y. Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP. Carcinogenesis, 2001, 22(9), 1399-1403. doi: 10.1093/carcin/22.9.1399 PMID: 11532861
  60. Moher, D; Liberati, A; Tetzlaff, J; Altman, DG Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann. Intern. Med., 2009, 151(4), 264-9, w64.
  61. Nambiar, D.K.; Rajamani, P.; Deep, G.; Jain, A.K.; Agarwal, R.; Singh, R.P. Silibinin preferentially radiosensitizes prostate cancer by inhibiting DNA repair signaling. Mol. Cancer Ther., 2015, 14(12), 2722-2734. doi: 10.1158/1535-7163.MCT-15-0348 PMID: 26516160
  62. Nambiar, D.K.; Rajamani, P.; Singh, R.P. Silibinin attenuates ionizing radiation-induced pro-angiogenic response and EMT in prostate cancer cells. Biochem. Biophys. Res. Commun., 2015, 456(1), 262-268. doi: 10.1016/j.bbrc.2014.11.069 PMID: 25446081
  63. Lal, M.; Gupta, D. Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells. Discoveries, 2016, 4(1), e56. doi: 10.15190/d.2016.3 PMID: 32309577
  64. Prack Mc Cormick, B.; Langle, Y.; Belgorosky, D.; Vanzulli, S.; Balarino, N.; Sandes, E.; Eiján, A.M. Flavonoid silybin improves the response to radiotherapy in invasive bladder cancer. J. Cell. Biochem., 2018, 119(7), 5402-5412. doi: 10.1002/jcb.26693 PMID: 29363820
  65. Bilgic, E.; Tuncel, N.; Koca, T. Radio-sensitivity on MCF-7 cells of silver nanoparticles synthesized by Silybum marianum; Inorgan Nano-Met Chem, 2021, pp. 1-9.
  66. Rajput, M.; Mishra, D.; Kumar, K.; Singh, R.P. Silibinin radiosensitizes egf receptor-knockdown prostate cancer cells by attenuating DNA repair pathways. J. Cancer Prev., 2022, 27(3), 170-181. doi: 10.15430/JCP.2022.27.3.170 PMID: 36258717
  67. Lal, M.; Ahmad Khan, S.; Gupta, D. Silymarin mediates apoptosis through activation of jnk/erk signaling pathway in human colon carcinoma cells in response to ( 60 Co) gamma radiation. Acta Scientific Cancer Biology, 2022, 6(6), 01-13. doi: 10.31080/ASCB.2022.06.0388
  68. Latacela, G.A.; Ramaiah, P.; Patra, I.; Jalil, A.T.; Gupta, R.; Madaminov, F.A.; Shaker Shafik, S.; Al-Gazally, M.E.; Ansari, M.J.; Kandeel, M.; Mustafa, Y.F.; Farhood, B. The radioprotective potentials of silymarin/silibinin against radiotherapy- induced toxicities: A systematic review of clinical and experimental studies. Curr. Med. Chem., 2023, 30(33), 3775-3797. doi: 10.2174/0929867330666221124155339 PMID: 36424777
  69. Ghodousi, M.; Karbasforooshan, H.; Arabi, L.; Elyasi, S. Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: A comprehensive review of preclinical and clinical data. Eur. J. Clin. Pharmacol., 2023, 79(1), 15-38. doi: 10.1007/s00228-022-03434-8 PMID: 36450892
  70. Ramadan, L.A.; Roushdy, H.M.; Abu Senna, G.M.; Amin, N.E.; El-Deshw, O.A. Radioprotective effect of silymarin against radiation induced hepatotoxicity. Pharmacol. Res., 2002, 45(6), 447-454. doi: 10.1006/phrs.2002.0990 PMID: 12162944
  71. Tiwari, P.; Kumar, A.; Ali, M.; Mishra, K.P. Radioprotection of plasmid and cellular DNA and Swiss mice by silibinin. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2010, 695(1-2), 55-60. doi: 10.1016/j.mrgentox.2009.11.007 PMID: 19945544
  72. Becker-Schiebe, M.; Mengs, U.; Schaefer, M.; Bulitta, M.; Hoffmann, W. Topical use of a silymarin-based preparation to prevent radiodermatitis : Results of a prospective study in breast cancer patients. Strahlenther. Onkol., 2011, 187(8), 485-491. doi: 10.1007/s00066-011-2204-z PMID: 21786113
  73. Son, Y.; Lee, H.J.; Rho, J.K.; Chung, S.Y.; Lee, C.G.; Yang, K.; Kim, S.H.; Lee, M.; Shin, I.S.; Kim, J.S. The ameliorative effect of silibinin against radiation-induced lung injury: Protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulm. Med., 2015, 15(1), 68. doi: 10.1186/s12890-015-0055-6 PMID: 26143275
  74. Adhikari, M.; Arora, R. The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity. Environ. Toxicol., 2016, 31(6), 641-654. doi: 10.1002/tox.22076 PMID: 25411116
  75. Kim, J.S.; Han, N.K.; Kim, S.H.; Lee, H.J. Silibinin attenuates radiation-induced intestinal fibrosis and reverses epithelial-to-mesenchymal transition. Oncotarget, 2017, 8(41), 69386-69397. doi: 10.18632/oncotarget.20624 PMID: 29050211
  76. Elyasi, S.; Hosseini, S.; Niazi Moghadam, M.R.; Aledavood, S.A.; Karimi, G. Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: A randomized, double-blinded, placebo-controlled clinical trial. Phytother. Res., 2016, 30(11), 1879-1885. doi: 10.1002/ptr.5704 PMID: 27555604
  77. Fatehi, D.; Mohammadi, M.; Shekarchi, B.; Shabani, A.; Seify, M.; Rostamzadeh, A. Radioprotective effects of Silymarin on the sperm parameters of NMRI mice irradiated with γ-rays. J. Photochem. Photobiol. B, 2018, 178, 489-495. doi: 10.1016/j.jphotobiol.2017.12.004 PMID: 29232573
  78. Karbasforooshan, H.; Hosseini, S.; Elyasi, S.; Fani Pakdel, A.; Karimi, G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2019, 33(2), 379-386. doi: 10.1002/ptr.6231 PMID: 30479044
  79. Mohamed, M.A.E.H.; Mohammed, H.S.; Mostafa, S.A.; Ibrahim, M.T. Protective effects of Saraca indica L. leaves extract (family Fabaceae) against gamma irradiation induced injury in the kidney of female albino rats. Environ. Toxicol., 2021, 36(4), 506-519. doi: 10.1002/tox.23056 PMID: 33166054
  80. Dheeraj, A.; Tailor, D.; Singh, S.P.; Singh, R.P. Anticancer attributes of silibinin: Chemo-and radiosensitization of cancer. In: Role of Nutraceuticals in Cancer Chemosensitization; Elsevier, 2018; pp. 199-220.
  81. Wang, J.; Wang, H.; Qian, H. Biological effects of radiation on cancer cells. Mil. Med. Res., 2018, 5(1), 20. doi: 10.1186/s40779-018-0167-4 PMID: 29958545
  82. Ashrafizadeh, M.; Farhood, B.; Eleojo Musa, A.; Taeb, S.; Najafi, M. The interactions and communications in tumor resistance to radiotherapy: Therapy perspectives. Int. Immunopharmacol., 2020, 87, 106807. doi: 10.1016/j.intimp.2020.106807 PMID: 32683299
  83. Iliakis, G.; Wang, Y.; Guan, J.; Wang, H. DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene, 2003, 22(37), 5834-5847. doi: 10.1038/sj.onc.1206682 PMID: 12947390
  84. Prise, K.M.; Schettino, G.; Folkard, M.; Held, K.D. New insights on cell death from radiation exposure. Lancet Oncol., 2005, 6(7), 520-528. doi: 10.1016/S1470-2045(05)70246-1 PMID: 15992701
  85. Lee, S.Y.; Jeong, E.K.; Ju, M.K.; Jeon, H.M.; Kim, M.Y.; Kim, C.H.; Park, H.G.; Han, S.I.; Kang, H.S. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol. Cancer, 2017, 16(1), 10. doi: 10.1186/s12943-016-0577-4 PMID: 28137309
  86. Cheung, C.W.; Vesey, D.A.; Nicol, D.L.; Johnson, D.W. Silibinin inhibits renal cell carcinoma via mechanisms that are independent of insulin-like growth factor-binding protein 3. BJU Int., 2007, 99(2), 454-460. doi: 10.1111/j.1464-410X.2007.06571.x PMID: 17313429
  87. Bhatia, N.; Zhao, J.; Wolf, D.M.; Agarwal, R. Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: Comparison with silymarin. Cancer Lett., 1999, 147(1-2), 77-84. doi: 10.1016/S0304-3835(99)00276-1 PMID: 10660092
  88. Cui, H.; Li, T.L.; Guo, H.F.; Wang, J.L.; Xue, P.; Zhang, Y.; Fan, J.H.; Li, Z.P.; Gao, Y.J. Silymarin-mediated regulation of the cell cycle and DNA damage response exerts antitumor activity in human hepatocellular carcinoma. Oncol. Lett., 2018, 15(1), 885-892. PMID: 29399153
  89. Yurtcu, E.; İşeri, Ö.D.; Sahin, F.I. Genotoxic and cytotoxic effects of doxorubicin and silymarin on human hepatocellular carcinoma cells. Hum. Exp. Toxicol., 2014, 33(12), 1269-1276. doi: 10.1177/0960327114529453 PMID: 24677352
  90. Deep, G.; Singh, R.P.; Agarwal, C.; Kroll, D.J.; Agarwal, R. Silymarin and silibinin cause G1 and G2–M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: A comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene, 2006, 25(7), 1053-1069. doi: 10.1038/sj.onc.1209146 PMID: 16205633
  91. Ashrafizadeh, M.; Taeb, S.; Haghi-Aminjan, H.; Afrashi, S.; Moloudi, K.; Musa, A.E.; Najafi, M.; Farhood, B. Resveratrol as an enhancer of apoptosis in cancer: A mechanistic review. Anticancer. Agents Med. Chem., 2021, 21(17), 2327-2336. doi: 10.2174/1871520620666201020160348 PMID: 33081687
  92. Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Potes, Y.; Shabeeb, D.; Musa, A.E. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review. Life Sci., 2019, 228, 228-241. doi: 10.1016/j.lfs.2019.05.009 PMID: 31077716
  93. Jang, J.S.; Kim, K.M.; Kang, K.H.; Choi, J.E.; Lee, W.K.; Kim, C.H.; Kang, Y.M.; Kam, S.; Kim, I.S.; Jun, J.E.; Jung, T.H.; Park, J.Y. Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer, 2008, 60(1), 31-39. doi: 10.1016/j.lungcan.2007.09.008 PMID: 17961802
  94. Akbari-Kordkheyli, V; Abbaszadeh-Goudarzi, K; Nejati-Laskokalayeh, M; Zarpou, S; Khonakdar-Tarsi, A The protective effects of silymarin on ischemia-reperfusion injuries: A mechanistic review. Iran J Basic Med Sci., 2019, 22(9), 968.
  95. Fischer, T.W.; Zmijewski, M.A.; Wortsman, J.; Slominski, A. Melatonin maintains mitochondrial membrane potential and attenuates activation of initiator (casp-9) and effector caspases (casp-3/casp-7) and PARP in UVR-exposed HaCaT keratinocytes. J. Pineal Res., 2008, 44(4), 397-407. doi: 10.1111/j.1600-079X.2007.00542.x PMID: 18086147
  96. Moutabian, H.; Majdaeen, M.; Ghahramani-Asl, R.; Yadollahi, M.; Gharepapagh, E.; Ataei, G.; Falahatpour, Z.; Bagheri, H.; Farhood, B. A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: with a special focus on the oxidant, apoptotic, and anti-inflammatory activities. Cancer Cell Int., 2022, 22(1), 142. doi: 10.1186/s12935-022-02561-7 PMID: 35366874
  97. Wu, X-Y.; Zhai, J.; Huan, X-K.; Xu, W-W.; Tian, J.; Farhood, B. A systematic review of the therapeutic potential of resveratrol during colorectal cancer chemotherapy. Mini Rev. Med. Chem., 2022. PMID: 36173048
  98. Santivasi, W.L.; Xia, F. Ionizing radiation-induced DNA damage, response, and repair. Antioxid. Redox Signal., 2014, 21(2), 251-259. doi: 10.1089/ars.2013.5668 PMID: 24180216
  99. Surova, O.; Zhivotovsky, B. Various modes of cell death induced by DNA damage. Oncogene, 2013, 32(33), 3789-3797. doi: 10.1038/onc.2012.556 PMID: 23208502
  100. Gudkov, A.V.; Komarova, E.A. The role of p53 in determining sensitivity to radiotherapy. Nat. Rev. Cancer, 2003, 3(2), 117-129. doi: 10.1038/nrc992 PMID: 12563311
  101. Fei, P.; El-Deiry, W.S. P53 and radiation responses. Oncogene, 2003, 22(37), 5774-5783. doi: 10.1038/sj.onc.1206677 PMID: 12947385
  102. Adhya, AK; Srinivasan, R; Patel, FD Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix. Int. J. Gynecol. Pathol., 2006, 25(3), 281-287.
  103. Sakakura, C.; Sweeney, E.A.; Shirahama, T.; Igarashi, Y.; Hakomori, S.; Nakatani, H.; Tsujimoto, H.; Imanishi, T.; Ohgaki, M.; Ohyama, T.; Yamazaki, J.; Hagiwara, A.; Yamaguchi, T.; Sawai, K.; Takahashi, T. Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis. Int. J. Cancer, 1996, 67(1), 101-105. doi: 10.1002/(SICI)1097-0215(19960703)67:13.0.CO;2-H PMID: 8690508
  104. Jänicke, R.U.; Sprengart, M.L.; Wati, M.R.; Porter, A.G. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem., 1998, 273(16), 9357-9360. doi: 10.1074/jbc.273.16.9357 PMID: 9545256
  105. Gondo, H.K. The effect of spirulina on apoptosis through the caspase-3 pathway in a Preeclamptic Wistar rat model. J. Nat. Sci. Biol. Med., 2021, 12(3), 280-284.
  106. Yardım, A.; Kucukler, S.; Özdemir, S.; Çomaklı, S.; Caglayan, C.; Kandemir, F.M.; Çelik, H. Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Gene, 2021, 769, 145239. doi: 10.1016/j.gene.2020.145239 PMID: 33069805
  107. Su, C. Survivin in survival of hepatocellular carcinoma. Cancer Lett., 2016, 379(2), 184-190. doi: 10.1016/j.canlet.2015.06.016 PMID: 26118774
  108. Rödel, F.; Hoffmann, J.; Distel, L.; Herrmann, M.; Noisternig, T.; Papadopoulos, T.; Sauer, R.; Rödel, C. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res., 2005, 65(11), 4881-4887. doi: 10.1158/0008-5472.CAN-04-3028 PMID: 15930309
  109. Mobahat, M.; Narendran, A.; Riabowol, K. Survivin as a preferential target for cancer therapy. Int. J. Mol. Sci., 2014, 15(2), 2494-2516. doi: 10.3390/ijms15022494 PMID: 24531137
  110. Vaid, M.; Singh, T.; Prasad, R.; Katiyar, S.K. Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis. Mol. Carcinog., 2015, 54(11), 1328-1339. doi: 10.1002/mc.22208 PMID: 25174976
  111. Fan, L.; Ma, Y.; Liu, Y.; Zheng, D.; Huang, G. Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. Eur. J. Pharmacol., 2014, 743, 79-88. doi: 10.1016/j.ejphar.2014.09.019 PMID: 25242120
  112. Kim, K.W.; Choi, C.H.; Kim, T.H.; Kwon, C.H.; Woo, J.S.; Kim, Y.K. Silibinin inhibits glioma cell proliferation via Ca2+/ROS/MAPK-dependent mechanism in vitro and glioma tumor growth in vivo. Neurochem. Res., 2009, 34(8), 1479-1490. doi: 10.1007/s11064-009-9935-6 PMID: 19263218
  113. Singh, R.P.; Raina, K.; Sharma, G.; Agarwal, R. Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice. Clin. Cancer Res., 2008, 14(23), 7773-7780. doi: 10.1158/1078-0432.CCR-08-1309 PMID: 19047104
  114. Wang, Y.X.; Cai, H.; Jiang, G.; Zhou, T.B.; Wu, H. Silibinin inhibits proliferation, induces apoptosis and causes cell cycle arrest in human gastric cancer MGC803 cells via STAT3 pathway inhibition. Asian Pac. J. Cancer Prev., 2014, 15(16), 6791-6798. doi: 10.7314/APJCP.2014.15.16.6791 PMID: 25169527
  115. Won, D.H.; Kim, L.H.; Jang, B.; Yang, I.H.; Kwon, H.J.; Jin, B.; Oh, S.H.; Kang, J.H.; Hong, S.D.; Shin, J.A.; Cho, S.D. In vitro and in vivo anti-cancer activity of silymarin on oral cancer. Tumour Biol., 2018, 40(5) doi: 10.1177/1010428318776170 PMID: 29764340
  116. Nambiar, D.; Prajapati, V.; Agarwal, R.; Singh, R.P. In vitro and in vivo anticancer efficacy of silibinin against human pancreatic cancer BxPC-3 and PANC-1 cells. Cancer Lett., 2013, 334(1), 109-117. doi: 10.1016/j.canlet.2012.09.004 PMID: 23022268
  117. Wang, Y.; Yuan, A.J.; Wu, Y.J.; Wu, L.M.; Zhang, L. Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations. J. Funct. Foods, 2023, 100, 105384. doi: 10.1016/j.jff.2022.105384
  118. Mashhadi, A.B.M.; Mashhadi, A.B.M.; Golmohammad, S. Overview of Silibinin anti-tumor effects. J. Herb. Med., 2020, 23, 100375. doi: 10.1016/j.hermed.2020.100375
  119. Shi, W; Hou, X; Bao, X; Hou, W; Jiang, X; Ma, L Mechanism and protection of radiotherapy induced sensorineural hearing loss for head and neck cancer. Biomed Res Int., 2021, 2021, 3548706. doi: 10.1155/2021/3548706
  120. Brown, L.; Benchimol, S. The involvement of MAPK signaling pathways in determining the cellular response to p53 activation: cell cycle arrest or apoptosis. J. Biol. Chem., 2006, 281(7), 3832-3840. doi: 10.1074/jbc.M507951200 PMID: 16330547
  121. Hariyanti, T.; Margiana, R.; Al-Gazally, M.E.; Patra, I.; Lateef Al-Awsi, G.R.; Hameed, N.; Kayumova, D.; Ansari, M.J.; Torres-Criollo, L.M.; Mustafa, Y.F.; Abedi-Firouzjah, R.; Farhood, B. The protective effects of silymarin on the reproductive toxicity: A comprehensive review. Curr. Med. Chem., 2023, 30(39), 4421-4449. doi: 10.2174/0929867330666230130115332 PMID: 36717999
  122. Hoxhaj, G.; Manning, B.D. The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nat. Rev. Cancer, 2020, 20(2), 74-88. doi: 10.1038/s41568-019-0216-7 PMID: 31686003
  123. Li, H.F.; Kim, J.S.; Waldman, T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat. Oncol., 2009, 4(1), 43. doi: 10.1186/1748-717X-4-43 PMID: 19828040
  124. Hein, A.L.; Ouellette, M.M.; Yan, Y. Radiation-induced signaling pathways that promote cancer cell survival (Review). Int. J. Oncol., 2014, 45(5), 1813-1819. doi: 10.3892/ijo.2014.2614 PMID: 25174607
  125. Marampon, F.; Ciccarelli, C.; Zani, B.M. Biological rationale for targeting MEK/ERK pathways in anti-cancer therapy and to potentiate tumour responses to radiation. Int. J. Mol. Sci., 2019, 20(10), 2530. doi: 10.3390/ijms20102530 PMID: 31126017
  126. Lee, K.B.; Kim, K-R.; Huh, T-L.; Lee, Y.M. Proton induces apoptosis of hypoxic tumor cells by the p53-dependent and p38/JNK MAPK signaling pathways. Int. J. Oncol., 2008, 33(6), 1247-1256. PMID: 19020758
  127. Choi, E.S.; Oh, S.; Jang, B.; Yu, H.J.; Shin, J.A.; Cho, N.P.; Yang, I.H.; Won, D.H.; Kwon, H.J.; Hong, S.D.; Cho, S.D. Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade. Cell Oncol., 2017, 40(3), 235-246. doi: 10.1007/s13402-017-0318-8 PMID: 28401485
  128. Singh, R.P.; Dhanalakshmi, S.; Mohan, S.; Agarwal, C.; Agarwal, R. Silibinin inhibits UVB- and epidermal growth factor–induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-κB in mouse epidermal JB6 cells. Mol. Cancer Ther., 2006, 5(5), 1145-1153. doi: 10.1158/1535-7163.MCT-05-0478 PMID: 16731746
  129. Bowman, T.; Garcia, R.; Turkson, J.; Jove, R. STATs in oncogenesis. Oncogene, 2000, 19(21), 2474-2488. doi: 10.1038/sj.onc.1203527 PMID: 10851046
  130. Bromberg, J.F. Activation of STAT proteins and growth control. BioEssays, 2001, 23(2), 161-169. doi: 10.1002/1521-1878(200102)23:23.0.CO;2-0 PMID: 11169589
  131. Bromberg, J. Stat proteins and oncogenesis. J. Clin. Invest., 2002, 109(9), 1139-1142. doi: 10.1172/JCI0215617 PMID: 11994401
  132. Epling-Burnette, P.K.; Liu, J.H.; Catlett-Falcone, R.; Turkson, J.; Oshiro, M.; Kothapalli, R.; Li, Y.; Wang, J.M.; Yang-Yen, H.F.; Karras, J.; Jove, R.; Loughran, T.P., Jr Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J. Clin. Invest., 2001, 107(3), 351-362. doi: 10.1172/JCI9940 PMID: 11160159
  133. Yu, H.; Jove, R. The STATs of cancer — new molecular targets come of age. Nat. Rev. Cancer, 2004, 4(2), 97-105. doi: 10.1038/nrc1275 PMID: 14964307
  134. Park, S.Y.; Lee, C.J.; Choi, J.H.; Kim, J.H.; Kim, J.W.; Kim, J.Y.; Nam, J.S. The JAK2/STAT3/CCND2 Axis promotes colorectal cancer stem cell persistence and radioresistance. J. Exp. Clin. Cancer Res., 2019, 38(1), 399. doi: 10.1186/s13046-019-1405-7 PMID: 31511084
  135. Lu, L.; Dong, J.; Wang, L.; Xia, Q.; Zhang, D.; Kim, H.; Yin, T.; Fan, S.; Shen, Q. Activation of STAT3 and Bcl-2 and reduction of reactive oxygen species (ROS) promote radioresistance in breast cancer and overcome of radioresistance with niclosamide. Oncogene, 2018, 37(39), 5292-5304. doi: 10.1038/s41388-018-0340-y PMID: 29855616
  136. Li, F.; Gao, L.; Wang, Z.; Dong, B.; Yan, T.; Jiang, Q.; Chen, X. Radiation enhances the invasion abilities of pulmonary adenocarcinoma cells via STAT3. Mol. Med. Rep., 2013, 7(6), 1883-1888. doi: 10.3892/mmr.2013.1441 PMID: 23620191
  137. Singh-Gupta, V.; Zhang, H.; Banerjee, S.; Kong, D.; Raffoul, J.J.; Sarkar, F.H.; Hillman, G.G. Radiation-induced HIF-1α cell survival pathway is inhibited by soy isoflavones in prostate cancer cells. Int. J. Cancer, 2009, 124(7), 1675-1684. doi: 10.1002/ijc.24015 PMID: 19101986
  138. Wang, X.; Zhang, X.; Qiu, C.; Yang, N. STAT3 contributes to radioresistance in cancer. Front. Oncol., 2020, 10, 1120. doi: 10.3389/fonc.2020.01120 PMID: 32733808
  139. Gaur, P.; Bose, D.; Samuel, S.; Ellis, L.M. Eds.; Targeting tumor angiogenesis. In: Seminars in oncology; Elsevier, 2009.
  140. Kanthou, C.; Tozer, G. Targeting the vasculature of tumours: Combining VEGF pathway inhibitors with radiotherapy. Br. J. Radiol., 2019, 92(1093), 20180405. PMID: 30160184
  141. Bachtiary, B.; Selzer, E.; Knocke, T.H.; Pötter, R.; Obermair, A. Serum VEGF levels in patients undergoing primary radiotherapy for cervical cancer: impact on progression-free survival. Cancer Lett., 2002, 179(2), 197-203. doi: 10.1016/S0304-3835(01)00872-2 PMID: 11888674
  142. Chen, HH; Su, W-C; Chou, C-Y; Guo, H-R; Ho, S-Y; Que, J Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy. Int. J. Radiat. Oncol Biol. Phys., 2005, 63(4), 1093-100. doi: 10.1016/j.ijrobp.2005.03.062
  143. Solberg, TD; Nearman, J; Mullins, J; Li, S; Baranowska-Kortylewicz, J Correlation between tumor growth delay and expression of cancer and host VEGF, VEGFR2, and osteopontin in response to radiotherapy. Int. J. Radiat. Oncol. Biol. Phys., 2008, 72(3), 918-926.
  144. Kleibeuker, E.A.; Griffioen, A.W.; Verheul, H.M.; Slotman, B.J.; Thijssen, V.L. Combining angiogenesis inhibition and radiotherapy: A double-edged sword. Drug Resist. Updat., 2012, 15(3), 173-182. doi: 10.1016/j.drup.2012.04.002 PMID: 22561672
  145. Sonveaux, P.; Brouet, A.; Havaux, X.; Grégoire, V.; Dessy, C.; Balligand, J-L.; Feron, O. Irradiation-induced angiogenesis through the up-regulation of the nitric oxide pathway: Implications for tumor radiotherapy. Cancer Res., 2003, 63(5), 1012-1019. PMID: 12615716
  146. Deep, G.; Gangar, S.C.; Rajamanickam, S.; Raina, K.; Gu, M.; Agarwal, C.; Oberlies, N.H.; Agarwal, R. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: Targeting VEGF-VEGFR signaling. PLoS One, 2012, 7(4), e34630. doi: 10.1371/journal.pone.0034630 PMID: 22514647
  147. Deep, G.; Raina, K.; Singh, R.P.; Oberlies, N.H.; Kroll, D.J.; Agarwal, R. Isosilibinin inhibits advanced human prostate cancer growth in athymic nude mice: Comparison with silymarin and silibinin. Int. J. Cancer, 2008, 123(12), 2750-2758. doi: 10.1002/ijc.23879 PMID: 18798272
  148. Singh, R.P.; Sharma, G.; Dhanalakshmi, S.; Agarwal, C.; Agarwal, R. Suppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis. Cancer Epidemiol. Biomarkers Prev., 2003, 12(9), 933-939. PMID: 14504208
  149. Tyagi, A.; Agarwal, C.; Dwyer-Nield, L.D.; Singh, R.P.; Malkinson, A.M.; Agarwal, R. Silibinin modulates TNF-α and IFN-γ mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Mol. Carcinog., 2012, 51(10), 832-842. doi: 10.1002/mc.20851 PMID: 21882257
  150. Singh, R.P.; Deep, G.; Chittezhath, M.; Kaur, M.; Dwyer-Nield, L.D.; Malkinson, A.M.; Agarwal, R. Effect of silibinin on the growth and progression of primary lung tumors in mice. J. Natl. Cancer Inst., 2006, 98(12), 846-855. doi: 10.1093/jnci/djj231 PMID: 16788158
  151. Ramasamy, K.; Dwyer-Nield, L.D.; Serkova, N.J.; Hasebroock, K.M.; Tyagi, A.; Raina, K.; Singh, R.P.; Malkinson, A.M.; Agarwal, R. Silibinin prevents lung tumorigenesis in wild-type but not in iNOS-/- mice: potential of real-time micro-CT in lung cancer chemoprevention studies. Clin. Cancer Res., 2011, 17(4), 753-761. doi: 10.1158/1078-0432.CCR-10-2290 PMID: 21148748
  152. Yang, S.H.; Lin, J.K.; Chen, W.S.; Chiu, J.H. Anti-angiogenic effect of silymarin on colon cancer lovo cell line. J. Surg. Res., 2003, 113(1), 133-138. doi: 10.1016/S0022-4804(03)00229-4 PMID: 12943822
  153. García-Maceira, P.; Mateo, J. Silibinin inhibits hypoxia-inducible factor-1α and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene, 2009, 28(3), 313-324. doi: 10.1038/onc.2008.398 PMID: 18978810
  154. Miyazawa, M.; Yasuda, M.; Miyazawa, M.; Ogane, N.; Katoh, T.; Yano, M.; Hirasawa, T.; Mikami, M.; Ishimoto, H. Hypoxia-inducible factor-1α suppression in ovarian clear-cell carcinoma cells by silibinin administration. Anticancer Res., 2020, 40(12), 6791-6798. doi: 10.21873/anticanres.14702 PMID: 33288572
  155. Tsai, J.H.; Yang, J. Epithelial–mesenchymal plasticity in carcinoma metastasis. Genes Dev., 2013, 27(20), 2192-2206. doi: 10.1101/gad.225334.113 PMID: 24142872
  156. Weber, G.F. Why does cancer therapy lack effective anti-metastasis drugs? Cancer Lett., 2013, 328(2), 207-211. doi: 10.1016/j.canlet.2012.09.025 PMID: 23059758
  157. Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med., 2013, 19(11), 1423-1437. doi: 10.1038/nm.3394 PMID: 24202395
  158. Wu, M.; Wang, G.; Hu, W.; Yao, Y.; Yu, X.F. Emerging roles and therapeutic value of exosomes in cancer metastasis. Mol. Cancer, 2019, 18(1), 53. doi: 10.1186/s12943-019-0964-8 PMID: 30925925
  159. Bakir, B.; Chiarella, A.M.; Pitarresi, J.R.; Rustgi, A.K. EMT, MET, plasticity, and tumor metastasis. Trends Cell Biol., 2020, 30(10), 764-776. doi: 10.1016/j.tcb.2020.07.003 PMID: 32800658
  160. Craene, B.D.; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer, 2013, 13(2), 97-110. doi: 10.1038/nrc3447 PMID: 23344542
  161. Lamouille, S.; Xu, J.; Derynck, R. Molecular mechanisms of epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol., 2014, 15(3), 178-196. doi: 10.1038/nrm3758 PMID: 24556840
  162. Wild-Bode, C.; Weller, M.; Rimner, A.; Dichgans, J.; Wick, W. Sublethal irradiation promotes migration and invasiveness of glioma cells: Implications for radiotherapy of human glioblastoma. Cancer Res., 2001, 61(6), 2744-2750. PMID: 11289157
  163. Kawamoto, A.; Yokoe, T.; Tanaka, K.; Saigusa, S.; Toiyama, Y.; Yasuda, H.; Inoue, Y.; Miki, C.; Kusunoki, M. Radiation induces epithelial-mesenchymal transition in colorectal cancer cells. Oncol. Rep., 2012, 27(1), 51-57. PMID: 21971767
  164. Zhang, X.; Li, X.; Zhang, N.; Yang, Q.; Moran, M.S. Low doses ionizing radiation enhances the invasiveness of breast cancer cells by inducing epithelial–mesenchymal transition. Biochem. Biophys. Res. Commun., 2011, 412(1), 188-192. doi: 10.1016/j.bbrc.2011.07.074 PMID: 21810413
  165. Li, T.; Zeng, Z-C.; Wang, L.; Qiu, S-J.; Zhou, J-W.; Zhi, X-T.; Yu, H-H.; Tang, Z-Y. Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial–mesenchymal transition. Cancer Gene Ther., 2011, 18(9), 617-626. doi: 10.1038/cgt.2011.29 PMID: 21637307
  166. Vaid, M.; Prasad, R.; Sun, Q.; Katiyar, S.K. Silymarin targets β-catenin signaling in blocking migration/invasion of human melanoma cells. PLoS One, 2011, 6(7), e23000. doi: 10.1371/journal.pone.0023000 PMID: 21829575
  167. Chu, S.C.; Chiou, H.L.; Chen, P.N.; Yang, S.F.; Hsieh, Y.S. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol. Carcinog., 2004, 40(3), 143-149. doi: 10.1002/mc.20018
  168. Singh, T.; Prasad, R.; Katiyar, S.K. Therapeutic intervention of silymarin on the migration of non-small cell lung cancer cells is associated with the axis of multiple molecular targets including class 1 HDACs, ZEB1 expression, and restoration of miR-203 and E-cadherin expression. Am. J. Cancer Res., 2016, 6(6), 1287-1301. PMID: 27429844
  169. Kim, D.H.; Park, S.J.; Lee, S.Y.; Yoon, H.S.; Park, C.M. Silymarin attenuates invasion and migration through the regulation of epithelial-mesenchymal transition in Huh7 cells. Korean J Clin Lab Sci, 2018, 50(3), 337-344. doi: 10.15324/kjcls.2018.50.3.337
  170. Raina, K.; Rajamanickam, S.; Singh, R.P.; Deep, G.; Chittezhath, M.; Agarwal, R. Stage-specific inhibitory effects and associated mechanisms of silibinin on tumor progression and metastasis in transgenic adenocarcinoma of the mouse prostate model. Cancer Res., 2008, 68(16), 6822-6830. doi: 10.1158/0008-5472.CAN-08-1332 PMID: 18701508
  171. Ting, H.J.; Deep, G.; Jain, A.K.; Cimic, A.; Sirintrapun, J.; Romero, L.M.; Cramer, S.D.; Agarwal, C.; Agarwal, R. Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2. Mol. Carcinog., 2015, 54(9), 730-741. doi: 10.1002/mc.22135 PMID: 24615813
  172. Wu, K.; Ning, Z.; Zeng, J.; Fan, J.; Zhou, J.; Zhang, T.; Zhang, L.; Chen, Y.; Gao, Y.; Wang, B.; Guo, P.; Li, L.; Wang, X.; He, D. Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial–mesenchymal transition and stemness. Cell. Signal., 2013, 25(12), 2625-2633. doi: 10.1016/j.cellsig.2013.08.028 PMID: 24012496
  173. Sameri, S.; Saidijam, M.; Bahreini, F.; Najafi, R. Cancer chemopreventive activities of silibinin on colorectal cancer through regulation of E-cadherin/β-catenin pathway. Nutr. Cancer, 2021, 73(8), 1389-1399. doi: 10.1080/01635581.2020.1800764 PMID: 32748663
  174. Soleimani, V.; Delghandi, P.S.; Moallem, S.A.; Karimi, G. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytother. Res., 2019, 33(6), 1627-1638. doi: 10.1002/ptr.6361 PMID: 31069872
  175. Bijak, M. Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)—chemistry, bioavailability, and metabolism. Molecules, 2017, 22(11), 1942. doi: 10.3390/molecules22111942 PMID: 29125572
  176. Gillessen, A.; Schmidt, H.H.J. Silymarin as supportive treatment in liver diseases: A narrative review. Adv. Ther., 2020, 37(4), 1279-1301. doi: 10.1007/s12325-020-01251-y PMID: 32065376
  177. Amawi, H.; Hussein, N.A.; Karthikeyan, C.; Manivannan, E.; Wisner, A.; Williams, F.E.; Samuel, T.; Trivedi, P.; Ashby, C.R., Jr; Tiwari, A.K. HM015k, a novel silybin derivative, multi-targets metastatic ovarian cancer cells and is safe in zebrafish toxicity studies. Front. Pharmacol., 2017, 8, 498. doi: 10.3389/fphar.2017.00498 PMID: 28824426
  178. Kosina, P.; Kren, V.; Gebhardt, R.; Grambal, F.; Ulrichová, J.; Walterová, D. Antioxidant properties of silybin glycosides. Phytother. Res., 2002, 16(S1), S33-S39. doi: 10.1002/ptr.796 PMID: 11933137
  179. Dobiasová, S.; Řehořová, K.; Kučerová, D.; Biedermann, D.; Káňová, K.; Petrásková, L. Multidrug resistance modulation activity of silybin derivatives and their anti-inflammatory potential. Antioxidants, 2020, 9(5), 455. doi: 10.3390/antiox9050455
  180. Simánek, V.; Kubisch, J.; Sedmera, P.; Halada, P.; Gazák, R.; Skottová, N.; Kren, V. Chemoenzymatic preparation of oligoglycosides of silybin, the flavonolignan from Silybum marianum. Heterocycles, 2001, 54(2), 901-915. doi: 10.3987/COM-00-S(I)89
  181. Škottová, N.; ŠVagera, Z.; Večeřa, R.; Urbánek, K.; Jegorov, A.; Šimánek, V. Pharmacokinetic study of iodine-labeled silibinins in rat. Pharmacol. Res., 2001, 44(3), 247-253. doi: 10.1006/phrs.2001.0854 PMID: 11529693
  182. Plíšková, M.; Vondráček, J.; Křen, V.; Gažák, R.; Sedmera, P.; Walterová, D.; Psotová, J.; Šimánek, V.; Machala, M. Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation. Toxicology, 2005, 215(1-2), 80-89. doi: 10.1016/j.tox.2005.06.020 PMID: 16076518
  183. Roubalová, L.; Dinkova-Kostova, A.T.; Biedermann, D.; Křen, V.; Ulrichová, J.; Vrba, J. Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells. Fitoterapia, 2017, 119, 115-120. doi: 10.1016/j.fitote.2017.04.012 PMID: 28450126
  184. Pyszková, M.; Biler, M.; Biedermann, D.; Valentová, K.; Kuzma, M.; Vrba, J.; Ulrichová, J.; Sokolová, R.; Mojović, M.; Popović-Bijelić, A.; Kubala, M.; Trouillas, P.; Křen, V.; Vacek, J. Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity. Free Radic. Biol. Med., 2016, 90, 114-125. doi: 10.1016/j.freeradbiomed.2015.11.014 PMID: 26582372
  185. Yang, L.X.; Huang, K.X.; Li, H.B.; Gong, J.X.; Wang, F.; Feng, Y.B.; Tao, Q.F.; Wu, Y.H.; Li, X.K.; Wu, X.M.; Zeng, S.; Spencer, S.; Zhao, Y.; Qu, J. Design, synthesis, and examination of neuron protective properties of alkenylated and amidated dehydro-silybin derivatives. J. Med. Chem., 2009, 52(23), 7732-7752. doi: 10.1021/jm900735p PMID: 19673490
  186. Mizuno, M.; Mori, K.; Tsuchiya, K.; Takaki, T.; Misawa, T.; Demizu, Y.; Shibanuma, M.; Fukuhara, K. Design, synthesis, and biological activity of conformationally restricted analogues of silibinin. ACS Omega, 2020, 5(36), 23164-23174. doi: 10.1021/acsomega.0c02936 PMID: 32954167
  187. Zarrelli, A.; Romanucci, V.; Tuccillo, C.; Federico, A.; Loguercio, C.; Gravante, R.; Di Fabio, G. New silibinin glyco-conjugates: Synthesis and evaluation of antioxidant properties. Bioorg. Med. Chem. Lett., 2014, 24(22), 5147-5149. doi: 10.1016/j.bmcl.2014.10.023 PMID: 25442301
  188. Vue, B.; Zhang, S.; Zhang, X.; Parisis, K.; Zhang, Q.; Zheng, S.; Wang, G.; Chen, Q.H. Silibinin derivatives as anti-prostate cancer agents: Synthesis and cell-based evaluations. Eur. J. Med. Chem., 2016, 109, 36-46. doi: 10.1016/j.ejmech.2015.12.041 PMID: 26748997
  189. Rajnochová Svobodová, A.; Gabrielová, E.; Ulrichová, J.; Zálešák, B.; Biedermann, D.; Vostálová, J. A pilot study of the UVA-photoprotective potential of dehydrosilybin, isosilybin, silychristin, and silydianin on human dermal fibroblasts. Arch. Dermatol. Res., 2019, 311(6), 477-490. doi: 10.1007/s00403-019-01928-7 PMID: 31079190
  190. Drouet, S.; Doussot, J.; Garros, L.; Mathiron, D.; Bassard, S.; Favre-Réguillon, A.; Molinié, R.; Lainé, É.; Hano, C. Selective synthesis of 3-O-Palmitoyl-Silybin, a New-to-Nature flavonolignan with increased protective action against oxidative damages in lipophilic media. Molecules, 2018, 23(10), 2594. doi: 10.3390/molecules23102594 PMID: 30309022
  191. Chen, X.; Zenger, K.; Lupp, A.; Kling, B.; Heilmann, J.; Fleck, C.; Kraus, B.; Decker, M. Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo. J. Med. Chem., 2012, 55(11), 5231-5242. doi: 10.1021/jm300246n PMID: 22624880
  192. Tilley, C.; Deep, G.; Agarwal, C.; Wempe, M.F.; Biedermann, D.; Valentová, K.; Kren, V.; Agarwal, R. Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation. Mol. Carcinog., 2016, 55(1), 3-14. doi: 10.1002/mc.22253 PMID: 25492239
  193. Di Costanzo, A.; Angelico, R. Formulation strategies for enhancing the bioavailability of silymarin: The dtate of the art. Molecules, 2019, 24(11), 2155. doi: 10.3390/molecules24112155 PMID: 31181687
  194. He, J.; Hou, S.; Lu, W.; Zhu, L.; Feng, J. Preparation, pharmacokinetics and body distribution of silymarin-loaded solid lipid nanoparticles after oral administration. J. Biomed. Nanotechnol., 2007, 3(2), 195-202. doi: 10.1166/jbn.2007.024
  195. Yousaf, A.M.; Malik, U.R.; Shahzad, Y.; Mahmood, T.; Hussain, T. Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization. J. Pharm. Anal., 2019, 9(1), 34-39. doi: 10.1016/j.jpha.2018.09.003 PMID: 30740255
  196. Ibrahim, A.H.; Rosqvist, E.; Smått, J.H.; Ibrahim, H.M.; Ismael, H.R.; Afouna, M.I.; Samy, A.M.; Rosenholm, J.M. Formulation and optimization of lyophilized nanosuspension tablets to improve the physicochemical properties and provide immediate release of silymarin. Int. J. Pharm., 2019, 563, 217-227. doi: 10.1016/j.ijpharm.2019.03.064 PMID: 30946894
  197. Liang, J.; Liu, Y.; Liu, J.; Li, Z.; Fan, Q.; Jiang, Z.; Yan, F.; Wang, Z.; Huang, P.; Feng, N. Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD. J. Nanobiotechnology, 2018, 16(1), 64. doi: 10.1186/s12951-018-0391-9 PMID: 30176941
  198. Yang, G.; Zhao, Y.; Feng, N.; Zhang, Y.; Liu, Y.; Dang, B. Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids. Asian J. Pharm. Sci., 2015, 10(3), 194-202. doi: 10.1016/j.ajps.2014.12.001
  199. Nasr, S.S.; Nasra, M.M.A.; Hazzah, H.A.; Abdallah, O.Y. Mesoporous silica nanoparticles, a safe option for silymarin delivery: Preparation, characterization, and in vivo evaluation. Drug Deliv. Transl. Res., 2019, 9(5), 968-979. doi: 10.1007/s13346-019-00640-3 PMID: 31001719
  200. Nagi, A.; Iqbal, B.; Kumar, S.; Sharma, S.; Ali, J.; Baboota, S. Quality by design based silymarin nanoemulsion for enhancement of oral bioavailability. J. Drug Deliv. Sci. Technol., 2017, 40, 35-44. doi: 10.1016/j.jddst.2017.05.019
  201. Piazzini, V.; Rosseti, C.; Bigagli, E.; Luceri, C.; Bilia, A.; Bergonzi, M. Prediction of permeation and cellular transport of Silybum marianum extract formulated in a nanoemulsion by using PAMPA and Caco-2 cell models. Planta Med., 2017, 83(14/15), 1184-1193. doi: 10.1055/s-0043-110052 PMID: 28472840
  202. Woo, J.S.; Kim, T.S.; Park, J.H.; Chi, S.C. Formulation and biopharmaceutical evaluation of silymarin using SMEDDS. Arch. Pharm. Res., 2007, 30(1), 82-89. doi: 10.1007/BF02977782 PMID: 17328246
  203. El-Far, M.; Salah, N.; Essam, A.; Abd El-Azim, A.O.; El-Sherbiny, I.M. Silymarin nanoformulation as potential anticancer agent in experimental Ehrlich ascites carcinoma-bearing animals. Nanomedicine, 2018, 13(15), 1865-1858. doi: 10.2217/nnm-2017-0394 PMID: 30136915
  204. Nguyen, M.H.; Yu, H.; Dong, B.; Hadinoto, K. A supersaturating delivery system of silibinin exhibiting high payload achieved by amorphous nano-complexation with chitosan. Eur. J. Pharm. Sci., 2016, 89, 163-171. doi: 10.1016/j.ejps.2016.04.036 PMID: 27140843
  205. Takke, A.; Shende, P. Nanotherapeutic silibinin: An insight of phytomedicine in healthcare reformation. Nanomedicine, 2019, 21, 102057. doi: 10.1016/j.nano.2019.102057 PMID: 31340181
  206. Tan, J.M.; Karthivashan, G.; Arulselvan, P.; Fakurazi, S.; Hussein, M.Z. Characterization and in vitro sustained release of silibinin from pH responsive carbon nanotube-based drug delivery system. J. Nanomater., 2014, 2014, 1.
  207. Adhikari, M.; Arora, R. Nano-silymarin provides protection against γ-radiation-induced oxidative stress in cultured human embryonic kidney cells. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2015, 792, 1-11. doi: 10.1016/j.mrgentox.2015.08.006 PMID: 26433256
  208. Azadpour, M.; Farajollahi, M.M.; Dariushnejad, H.; Varzi, A.M.; Varezardi, A.; Barati, M. Effects of synthetic silymarin-PLGA nanoparticles on M2 polarization and inflammatory cytokines in LPS-treated murine peritoneal macrophages. Iran. J. Basic Med. Sci., 2021, 24(10), 1446-1454. PMID: 35096304
  209. Mombeini, M.; Saki, G.; Khorsandi, L.; Bavarsad, N. Effects of silymarin-loaded nanoparticles on HT-29 human colon cancer cells. Medicina., 2018, 54(1), 1. doi: 10.3390/medicina54010001 PMID: 30344232
  210. Hosseini, S.; Rezaei, S.; Moghaddam, M.R.N.; Elyasi, S.; Karimi, G. Evaluation of oral nano-silymarin formulation efficacy on prevention of radiotherapy induced mucositis: A randomized, double-blinded, placebo-controlled clinical trial. PharmaNutrition, 2021, 15, 100253. doi: 10.1016/j.phanu.2021.100253
  211. Ghalehkhondabi, V.; Soleymani, M.; Fazlali, A. Folate-targeted nanomicelles containing silibinin as an active drug delivery system for liver cancer therapy. J. Drug Deliv. Sci. Technol., 2021, 61, 102157. doi: 10.1016/j.jddst.2020.102157
  212. Ripoli, M.; Angelico, R.; Sacco, P.; Ceglie, A.; Mangia, A. Phytoliposome-based silibinin delivery system as a promising strategy to prevent hepatitis c virus infection. J. Biomed. Nanotechnol., 2016, 12(4), 770-780. doi: 10.1166/jbn.2016.2161 PMID: 27301203

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers