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image of Milk Thistle (Silybum marianum): Potential Role in Cancer Prevention

Abstract

Milk thistle compounds have recently gained attention for their potential role in cancer prevention and treatment. Despite most evidence reporting this property refers to and animal studies, milk thistle flavonoids may provide insightful suggestions about novel chemopreventive agents. This narrative review provides an overview of the current understanding of milk thistle's effects on cancer cells and highlights possible mechanisms of action. The active compounds in milk thistle mainly exhibit antioxidant and anti-inflammatory effects, which protect cells and enhance their survival responses, even inhibiting cancer development. In addition, the compounds possess immunomodulatory properties crucial in preventing cancer progression. Another important mechanism is the induction of apoptosis, promoting cancer cell death and inhibiting tumour growth. These compounds inhibit angiogenesis, preventing tumour growth and spread. Due to their potential to inhibit cancer progression, they modulate cell signalling pathways, including the MAPK and PI3K/Akt pathways, which are involved in cell growth and survival. Although current research is promising, it is crucial to address the current gaps in knowledge about milk thistle compounds in cancer prevention and treatment. Future studies should focus on rigorous clinical trials, dose optimization, mechanistic investigations, combination therapy approaches, and personalized medicine to maximize their potential. Basic experimental evidence can provide new clues to establish clinical trials to improve cancer care and reassure patients and healthcare professionals.

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2025-05-06
2025-09-10

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References

  1. Singh R.P. Dhanalakshmi S. Tyagi A.K. Chan D.C. Agarwal C. Agarwal R. Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels. Cancer Res. 2002 62 11 3063 3069 12036915
    [Google Scholar]
  2. Das S.K. Vasudevan D.M. Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver. Indian J. Biochem. Biophys. 2006 43 5 306 311 17133738
    [Google Scholar]
  3. Albahri G. Badran A. Baki A.Z. Alame M. Hijazi A. Daou A. Baydoun E. Potential anti-tumorigenic properties of diverse medicinal plants against the majority of common types of cancer. Pharmaceuticals 2024 17 5 574 10.3390/ph17050574 38794144
    [Google Scholar]
  4. Shandiz F.A. Karimi G. Dayyani M. Hosseini S. Elyasi S. Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer. J. Oncol. Pharm. Pract. 2024 10781552241268778 10781552241268778 10.1177/10781552241268778 39110237
    [Google Scholar]
  5. Koláčková P. Růžičková G. Gregor T. Šišperová E. Quick method (FT-NIR) for the determination of oil and major fatty acids content in whole achenes of milk thistle (Silybum marianum (L.) Gaertn.). J. Sci. Food Agric. 2015 95 11 2264 2270 10.1002/jsfa.6945 25297972
    [Google Scholar]
  6. Jaggi A.S. Singh N. Silymarin and its role in chronic diseases. Adv. Exp. Med. Biol. 2016 929 25 44 10.1007/978‑3‑319‑41342‑6_2
    [Google Scholar]
  7. Lee D.Y.W. Liu Y. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J. Nat. Prod. 2003 66 9 1171 1174 10.1021/np030163b 14510591
    [Google Scholar]
  8. 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 10.1002/ptr.6361 31069872
    [Google Scholar]
  9. Fenclova M. Stranska-Zachariasova M. Benes F. Novakova A. Jonatova P. Kren V. Vitek L. Hajslova J. Liquid chromatography–drift tube ion mobility–mass spectrometry as a new challenging tool for the separation and characterization of silymarin flavonolignans. Anal. Bioanal. Chem. 2020 412 4 819 832 10.1007/s00216‑019‑02274‑3 31919606
    [Google Scholar]
  10. Abenavoli L. Capasso R. Milic N. Capasso F. Milk thistle in liver diseases: Past, present, future. Phytother. Res. 2010 24 10 1423 1432 10.1002/ptr.3207 20564545
    [Google Scholar]
  11. Nawaz A. Zaib S. Khan I. Ahmed A. Shahzadi K. Riaz H. Silybum marianum: An overview of its phytochemistry and pharmacological activities with emphasis on potential anticancer properties. Anticancer Agents Med. Chem. 2023 23 13 1519 1534 10.2174/1871520623666230412111152
    [Google Scholar]
  12. 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 10.1007/s00228‑022‑03434‑8 36450892
    [Google Scholar]
  13. Etemadi T. Momeni H.R. Darbandi N. Abnosi M.H. Silymarin modulates cadmium-induced oxidative stress in human spermatozoa. Andrologia 2022 54 8 e14475 10.1111/and.14475 35640054
    [Google Scholar]
  14. Schönfeld V. Weisbrod B. Müller M. Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cell. Mol. Life Sci. 2022 53 (11-12 917 920 10.1007/s000180050111 9447243
    [Google Scholar]
  15. Liakopoulou C. Kazazis C. Vallianou N.G. Silimarin and cancer. Anticancer Agents Med. Chem. 2018 18 14 1970 1974 10.2174/1871520618666180905154949
    [Google Scholar]
  16. Zi X. Agarwal R. Silibinin decreases prostate-specific antigen with cell growth inhibition via G 1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention. Proc. Natl. Acad. Sci. USA 1999 96 13 7490 7495 10.1073/pnas.96.13.7490 10377442
    [Google Scholar]
  17. Koltai T. Fliegel L. Role of silymarin in cancer treatment: Facts, hypotheses, and questions. J. Evid. Based Integr. Med. 2022 27 2515690X211068826 10.1177/2515690X211068826
    [Google Scholar]
  18. Duan L. Carrier D.J. Clausen E.C. Silymarin Extraction from Milk Thistle Using Hot Wate Proceedings of the Twenty-Fifth Symposium on Biotechnology for Fuels and Chemicals, Breckenridge, CO, May 4-7, 2003; Finkelstein, M.; McMillan, J.D.; Davison, B.H.; Evans, B., Eds.; Biotechnology for Fuels and Chemicals. Humana Press, Totowa, NJ, USA 2004 559 568 10.1007/978‑1‑59259‑837‑3_46
    [Google Scholar]
  19. Liu L. Zhang H. Milk thistle oil extracted by enzyme-mediated assisted solvent extraction compared with n-hexane and cold-pressed extraction. Molecules 2023 28 6 2591 10.3390/molecules28062591 36985564
    [Google Scholar]
  20. Xu C. Yuan Y. Pang P. Yang H. Zhang Q. Yuan D. Qi W. Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages. Biomed. Chromatogr. 2022 36 12 e5480 10.1002/bmc.5480 35962523
    [Google Scholar]
  21. Karimi G. Vahabzadeh M. Lari P. Rashedinia M. Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iran. J. Basic Med. Sci. 2011 14 4 308 317 23492971
    [Google Scholar]
  22. Brinda B.J. Zhu H.J. Markowitz J.S. A sensitive LC–MS/MS assay for the simultaneous analysis of the major active components of silymarin in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2012 902 1 9 10.1016/j.jchromb.2012.06.003 22766231
    [Google Scholar]
  23. Katiyar S. Silymarin and skin cancer prevention: Anti-inflammatory, antioxidant and immunomodulatory effects (Review). Int. J. Oncol. 2005 26 1 169 176 10.3892/ijo.26.1.169 15586237
    [Google Scholar]
  24. Imai-Sumida M. Chiyomaru T. Majid S. Saini S. Nip H. Dahiya R. Tanaka Y. Yamamura S. Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways. Oncotarget 2017 8 54 92032 92042 10.18632/oncotarget.20734 29190895
    [Google Scholar]
  25. Kalinowska M. Płońska A. Trusiak M. Gołębiewska E. Gorlewska-Pietluszenko A. Comparing the extraction methods, chemical composition, phenolic contents and antioxidant activity of edible oils from Cannabis sativa and Silybum marianu seeds. Sci. Rep. 2022 12 1 20609 10.1038/s41598‑022‑25030‑7 36446937
    [Google Scholar]
  26. Oliveira D.D.T. Sávio A.L.V. Marcondes C.D.J.P. Barros T.M. Barbosa L.C. Salvadori D.M.F. Silva D.G.N. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status. J. Biosci. 2017 42 1 91 101 10.1007/s12038‑016‑9654‑5 28229968
    [Google Scholar]
  27. Aghemo A. Alekseeva O.P. Angelico F. Bakulin I.G. Bakulina N.V. Bordin D. Bueverov A.O. Drapkina O.M. Gillessen A. Kagarmanova E.M. Korochanskaya N.V. Kucheryavii U.A. Lazebnik L.B. Livzan M.A. Maev I.V. Martynov A.I. Osipenko M.F. Sas E.I. Starodubova A. Uspensky Y.P. Vinnitskaya E.V. Yakovenko E.P. Yakovlev A.A. Role of silymarin as antioxidant in clinical management of chronic liver diseases: A narrative review. Ann. Med. 2022 54 1 1548 1560 10.1080/07853890.2022.2069854 35635048
    [Google Scholar]
  28. Veisi S. Johari S.A. Tyler C.R. Mansouri B. Esmaeilbeigi M. Antioxidant properties of dietary supplements of free and nanoencapsulated silymarin and their ameliorative effects on silver nanoparticles induced oxidative stress in Nile tilapia (Oreochromis niloticus). Environ. Sci. Pollut. Res. Int. 2021 28 20 26055 26063 10.1007/s11356‑021‑12568‑8 33483926
    [Google Scholar]
  29. Deep G. Oberlies N.H. Kroll D.J. Agarwal R. Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int. J. Cancer 2008 123 1 41 50 10.1002/ijc.23485 18435416
    [Google Scholar]
  30. Dhanalakshmi S. Agarwal C. Singh R.P. Agarwal R. Silibinin up-regulates DNA-protein kinase-dependent p53 activation to enhance UVB-induced apoptosis in mouse epithelial JB6 cells. J. Biol. Chem. 2005 280 21 20375 20383 10.1074/jbc.M414640200 15792956
    [Google Scholar]
  31. Kaur M. Agarwal R. Silymarin and epithelial cancer chemoprevention: How close we are to bedside? Toxicol. Appl. Pharmacol. 2007 224 3 350 359 10.1016/j.taap.2006.11.011 17184801
    [Google Scholar]
  32. Scavo M.P. Gentile E. Wolfram J. Gu J. Barone M. Evangelopoulos M. Martinez J.O. Liu X. Celia C. Tasciotti E. Vilar E. Shen H. Multistage vector delivery of sulindac and silymarin for prevention of colon cancer. Colloids Surf. B Biointerfaces 2015 136 694 703 10.1016/j.colsurfb.2015.10.005 26513752
    [Google Scholar]
  33. Alzoubi H.K. Khabour F.O. Alkofahi S.A. Mhaidat M.N. Abu-Siniyeh A.A. Anticancer and antimutagenic activity of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. against skin cancer induced by DMBA: In vitro and in vivo models. Pak. J. Pharm. Sci. 2021 34 3 987 993 34602423
    [Google Scholar]
  34. Khazaei R. Seidavi A. Bouyeh M. A review on the mechanisms of the effect of silymarin in milk thistle ( Silybum marianum ) on some laboratory animals. Vet. Med. Sci. 2022 8 1 289 301 10.1002/vms3.641 34599793
    [Google Scholar]
  35. Forghani P. Khorramizadeh M.R. Waller E.K. Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer. Cancer Med. 2014 3 2 215 224 10.1002/cam4.186 24574320
    [Google Scholar]
  36. Islam A. Mishra A. Siddiqui M.A. Siddiquie S. Recapitulation of evidence of phytochemical, pharmacokinetic and biomedical application of silybin. Drug Res. 2021 71 9 489 503 10.1055/a‑1528‑2721 34318464
    [Google Scholar]
  37. Boukazoula F. Ayari D. Effect of milk thistle ( Silybum marianum ) supplementation on the serum levels of oxidative stress markers in male half marathon athletes. Biomarkers 2022 27 5 461 469 10.1080/1354750X.2022.2056921 35315713
    [Google Scholar]
  38. Shankar V.K. Police A. Ajjarapu S. Murthy S.N. Development of silymarin topical formulation: In vitro and ex vivo dermal kinetics of silymarin. Int. J. Pharm. 2023 630 122431 10.1016/j.ijpharm.2022.122431 36436747
    [Google Scholar]
  39. Delmas D. Xiao J. Vejux A. Aires V. Silymarin and cancer: A dual strategy in both in chemoprevention and chemosensitivity. Molecules 2020 25 9 2009 10.3390/molecules25092009 32344919
    [Google Scholar]
  40. Kacar S. Aykanat B.N.E. Sahinturk V. Silymarin inhibited DU145 cells by activating SLIT2 protein and suppressing expression of CXCR4. Med. Oncol. 2020 37 3 18 10.1007/s12032‑020‑1343‑4 32062757
    [Google Scholar]
  41. Stolf A.M. Cardoso C.C. Morais H. Alves de Souza C.E. Lomba L.A. Brandt A.P. Agnes J.P. Collere F.C. Galindo C.M. Corso C.R. Spercoski K.M. Dittrich L.R. Zampronio A.R. Cadena S.M.S.C. Acco A. Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice. Biomed. Pharmacother. 2018 108 232 243 10.1016/j.biopha.2018.09.042 30219681
    [Google Scholar]
  42. Mateen S. Raina K. Agarwal C. Chan D. Agarwal R. Silibinin synergizes with histone deacetylase and DNA methyltransferase inhibitors in upregulating E-cadherin expression together with inhibition of migration and invasion of human non-small cell lung cancer cells. J. Pharmacol. Exp. Ther. 2013 345 2 206 214 10.1124/jpet.113.203471 23461975
    [Google Scholar]
  43. Dadar M. Shahali Y. Chakraborty S. Prasad M. Tahoori F. Tiwari R. Dhama K. Antiinflammatory peptides: Current knowledge and promising prospects. Inflamm. Res. 2019 68 2 125 145 10.1007/s00011‑018‑1208‑x 30560372
    [Google Scholar]
  44. El-Kamary S.S. Shardell M.D. Abdel-Hamid M. Ismail S. El-Ateek M. Metwally M. Mikhail N. Hashem M. Mousa A. Aboul-Fotouh A. El-Kassas M. Esmat G. Strickland G.T. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine 2009 16 5 391 400 10.1016/j.phymed.2009.02.002 19303273
    [Google Scholar]
  45. Surai P.F. Surai A. Earle-Payne K. Silymarin and inflammation: Food for thoughts. Antioxidants 2024 13 1 98 10.3390/antiox13010098 38247522
    [Google Scholar]
  46. Katiyar Katiyar S.K. Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review). Int. J. Oncol. 2010 36 5 1053 1060 10.3892/ijo_00000586 20372777
    [Google Scholar]
  47. Hu X. Qin N. Xue J. Li S. Huang X. Sun J. Xu F. Li Z. Li D. Hua H. Dehydrodiconiferyl alcohol from Silybum marianum (L.) Gaertn accelerates wound healing via inactivating NF-κB pathways in macrophages. J. Pharm. Pharmacol. 2020 72 2 305 317 10.1111/jphp.13205 31742713
    [Google Scholar]
  48. Kim S. Oh D.S. Oh J. Son T. Yuk D. Jung Y.S. Silymarin prevents restraint stress-induced acute liver injury by ameliorating oxidative stress and reducing inflammatory response. Molecules 2016 21 4 443 10.3390/molecules21040443 27043523
    [Google Scholar]
  49. Hoh C. Boocock D. Marczylo T. Singh R. Berry D.P. Dennison A.R. Hemingway D. Miller A. West K. Euden S. Garcea G. Farmer P.B. Steward W.P. Gescher A.J. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: Silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences. Clin. Cancer Res. 2006 12 9 2944 2950 10.1158/1078‑0432.CCR‑05‑2724 16675592
    [Google Scholar]
  50. 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 10.1177/1534735407302349 17548791
    [Google Scholar]
  51. Shahidi M. Vaziri F. Haerian A. Farzanegan A. Jafari S. Sharifi R. Shirazi F.S. Proliferative and anti-inflammatory effects of resveratrol and silymarin on human gingival fibroblasts: A view to the future. J. Dent. 2017 14 4 203 211 29285030
    [Google Scholar]
  52. Mandegary A. Saeedi A. Eftekhari A. Montazeri V. Sharif E. Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism. Daru 2013 21 1 28 10.1186/2008‑2231‑21‑28 23566372
    [Google Scholar]
  53. Křen V. Walterová D. Silybin and silymarin--new effects and applications. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc. Czech. Repub. 2005 149 1 29 41 10.5507/bp.2005.002
    [Google Scholar]
  54. Ramakrishnan G. Jagan S. Kamaraj S. Anandakumar P. Devaki T. Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis. Invest. New Drugs 2009 27 3 233 240 10.1007/s10637‑008‑9163‑y 18665326
    [Google Scholar]
  55. Murata N. Murakami K. Ozawa Y. Kinoshita N. Irie K. Shirasawa T. Shimizu T. Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer’s disease mouse model. Biosci. Biotechnol. Biochem. 2010 74 11 2299 2306 10.1271/bbb.100524 21071836
    [Google Scholar]
  56. Gheybi F. Rajabian F. Tayarani-Najaran Z. Adibi A.R. Alavizadeh S.H. Kesharwani P. Sahebkar A. Liposomal silymarin anti-oxidative and anti-apoptotic features in lung cells: An implication in cadmium toxicity. J. Trace Elem. Med. Biol. 2023 80 127291 10.1016/j.jtemb.2023.127291 37672872
    [Google Scholar]
  57. Fallah M. Davoodvandi A. Nikmanzar S. Aghili S. Mirazimi S.M.A. Aschner M. Rashidian A. Hamblin M.R. Chamanara M. Naghsh N. Mirzaei H. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomed. Pharmacother. 2021 142 112024 10.1016/j.biopha.2021.112024 34399200
    [Google Scholar]
  58. Yun D.G. Lee D.G. Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans. Int. J. Biochem. Cell Biol. 2016 80 1 9 10.1016/j.biocel.2016.09.008 27639679
    [Google Scholar]
  59. Pirouzpanah M.B. Sabzichi M. Pirouzpanah S. Chavoshi H. Samadi N. Silibilin-induces apoptosis in breast cancer cells by modulating p53, p21, Bak and Bcl-XL pathways. Asian Pac. J. Cancer Prev. 2015 16 5 2087 2092 10.7314/APJCP.2015.16.5.2087 25773855
    [Google Scholar]
  60. Aslan A. Can M.İ. Milk thistle impedes the development of carbontetrachloride-induced liver damage in rats through suppression of bcl-2 and regulating caspase pathway. Life Sci. 2014 117 1 13 18 10.1016/j.lfs.2014.09.005 25305509
    [Google Scholar]
  61. 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 10.1007/s13402‑017‑0318‑8 28401485
    [Google Scholar]
  62. Kropiwiec-Domańska K. Babicz M. Kędzierska-Matysek M. Szyndler-Nędza M. Skrzypczak E. Woliński B. Effect of milk thistle (Silybum marianum) supplementation on pork offal quality. Animals 2022 12 12 1526 10.3390/ani12121526 35739863
    [Google Scholar]
  63. MasodKhooy M.J. Farasat M. Salmi S.M. Mirzaei H. Combinatorial treatment with Silybum marianum essential oil enhances the therapeutic efficacy of a 5-fluorouracil base therapy for hepatocellular carcinoma. Phytother. Res. 2023 37 5 1968 1985 10.1002/ptr.7716 36788749
    [Google Scholar]
  64. 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 10.1371/journal.pone.0034630 22514647
    [Google Scholar]
  65. Addeo R. Silibinin: A New Opportunity for the Treatment of Brain Metastasis from Lung Cancer. J. Exp. Pharmacol. 2021 13 901 903 10.2147/JEP.S326871 34611448
    [Google Scholar]
  66. 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 10.1016/j.cellsig.2013.08.028 24012496
    [Google Scholar]
  67. 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 10.1093/jnci/djj231 16788158
    [Google Scholar]
  68. 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 10.1016/j.biopha.2016.04.039 27261626
    [Google Scholar]
  69. Amer M.E. Amer M.A. Othman A.I. Elsayed D.A. El-Missiry M.A. Ammar O.A. Silymarin inhibits the progression of Ehrlich solid tumor via targeting molecular pathways of cell death, proliferation, angiogenesis, and metastasis in female mice. Mol. Biol. Rep. 2022 49 6 4659 4671 10.1007/s11033‑022‑07315‑2 35305227
    [Google Scholar]
  70. 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 10.1002/mc.20018
    [Google Scholar]
  71. Singh R. Agarwal R. Prostate cancer prevention by silibinin. Curr. Cancer Drug Targets 2004 4 1 1 11 10.2174/1568009043481605 14965263
    [Google Scholar]
  72. Gharagozloo M. Jafari S. Esmaeil N. Javid E.N. Bagherpour B. Rezaei A. Immunosuppressive effect of silymarin on mitogen-activated protein kinase signalling pathway: The impact on T cell proliferation and cytokine production. Basic Clin. Pharmacol. Toxicol. 2013 113 3 209 214 10.1111/bcpt.12088 23701595
    [Google Scholar]
  73. Polyak S.J. Morishima C. Shuhart M.C. Wang C.C. Liu Y. Lee D.Y.W. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology 2007 132 5 1925 1936 10.1053/j.gastro.2007.02.038 17484885
    [Google Scholar]
  74. Yassin N.Y.S. AbouZid S.F. El-Kalaawy A.M. Ali T.M. Elesawy B.H. Ahmed O.M. Tackling of renal carcinogenesis in wistar rats by Silybum marianum total extract, silymarin, and silibinin via modulation of oxidative stress, apoptosis, Nrf2, PPAR γ, NF- κ B, and PI3K/Akt signaling pathways. Oxid. Med. Cell. Longev. 2021 2021 1 7665169 10.1155/2021/7665169 34630852
    [Google Scholar]
  75. Mulrow C. Lawrence V. Jacobs B. Dennehy C. Sapp J. Ramirez G. Aguilar C. Montgomery K. Morbidoni L. Arterburn J. In AHRQ evidence report summaries. United States Agency for Healthcare Research and Quality 2000
    [Google Scholar]
  76. Federico A. Dallio M. Loguercio C. Silymarin/silybin and chronic liver disease: A marriage of many years. Molecules 2017 22 2 191 10.3390/molecules22020191 28125040
    [Google Scholar]
  77. Yu L. Li T. Zhang H. Ma Z. Wu S. Silymarin suppresses proliferation of human hepatocellular carcinoma cells under hypoxia through downregulation of the HIF-1α/VEGF pathway. Am. J. Transl. Res. 2023 15 7 4521 4532 37560243
    [Google Scholar]
  78. Piscitelli S.C. Formentini E. Burstein A.H. Alfaro R. Jagannatha S. Falloon J. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002 22 5 551 556 10.1592/phco.22.8.551.33205 12013352
    [Google Scholar]
  79. Jacobs B.P. Dennehy C. Ramirez G. Sapp J. Lawrence V.A. Milk thistle for the treatment of liver disease. Am. J. Med. 2002 113 6 506 515 10.1016/S0002‑9343(02)01244‑5 12427501
    [Google Scholar]
  80. DiCenzo R. Shelton M. Jordan K. Koval C. Forrest A. Reichman R. Morse G. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy 2003 23 7 866 870 10.1592/phco.23.7.866.32723 12885100
    [Google Scholar]
  81. Gillessen A. Schmidt H.H.J. Silymarin as supportive treatment in liver diseases: A narrative review. Adv. Ther. 2020 37 4 1279 1301 10.1007/s12325‑020‑01251‑y 32065376
    [Google Scholar]
  82. Mills E. Wilson K. Clarke M. Foster B. Walker S. Rachlis B. DeGroot N. Montori V.M. Gold W. Phillips E. Myers S. Gallicano K. Milk thistle and indinavir: A randomized controlled pharmacokinetics study and meta-analysis. Eur. J. Clin. Pharmacol. 2005 61 1 1 7 10.1007/s00228‑004‑0843‑z 15666173
    [Google Scholar]
  83. Pradhan S.C. Girish C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J. Med. Res. 2006 124 5 491 504 17213517
    [Google Scholar]
  84. Saller R. Brignoli R. Melzer J. Meier R. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch. Komplementmed. 2008 15 1 9 20 10.1159/000113648
    [Google Scholar]
  85. Vidlar A. Vostalova J. Ulrichova J. Student V. Krajicek M. Vrbkova J. Simanek V. The safety and efficacy of a silymarin and selenium combination in men after radical prostatectomy - a six month placebo-controlled double-blind clinical trial. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2010 154 3 239 244 10.5507/bp.2010.036 21048810
    [Google Scholar]
  86. Wadhwa K. Pahwa R. Kumar M. Kumar S. Sharma P.C. Singh G. Verma R. Mittal V. Singh I. Kaushik D. Jeandet P. Mechanistic insights into the pharmacological significance of silymarin. Molecules 2022 27 16 5327 10.3390/molecules27165327 36014565
    [Google Scholar]
  87. Patel S. Waghela B. Shah K. Vaidya F. Mirza S. Patel S. Pathak C. Rawal R. Silibinin, a natural blend in polytherapy formulation for targeting Cd44v6 expressing colon cancer stem cells. Sci. Rep. 2018 8 1 16985 10.1038/s41598‑018‑35069‑0 30451890
    [Google Scholar]
  88. Marmouzi I. Bouyahya A. Ezzat S.M. Jemli E.M. Kharbach M. The food plant Silybum marianum (L.) Gaertn.: Phytochemistry, Ethnopharmacology and clinical evidence. J. Ethnopharmacol. 2021 265 113303 10.1016/j.jep.2020.113303 32877720
    [Google Scholar]
  89. Karbasforooshan H. Hosseini S. Elyasi S. Pakdel F.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 10.1002/ptr.6231 30479044
    [Google Scholar]
  90. Esfahani M.B.A.S. Reisi N. Mirmoghtadaei M. Evaluating the safety and efficacy of silymarin in β-thalassemia patients: A review. Hemoglobin 2015 39 2 75 80 10.3109/03630269.2014.1003224 25643967
    [Google Scholar]
  91. Kim J. Lee Y.N. Lee J. Lee S.G. Kim H. Choi Y.S. Draelos Z.D. Kim J. Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris: A prospective, open-label pilot study. J. Cosmet. Dermatol. 2023 22 2 561 568 10.1111/jocd.15439 36204969
    [Google Scholar]
  92. Siegel A.B. Narayan R. Rodriguez R. Goyal A. Jacobson J.S. Kelly K. Ladas E. Lunghofer P.J. Hansen R.J. Gustafson D.L. Flaig T.W. Tsai W.Y. Wu D.P. Lee V. Greenlee H. A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma. Integr. Cancer Ther. 2014 13 1 46 53 10.1177/1534735413490798 23757319
    [Google Scholar]
  93. Flaig T.W. Glodé M. Gustafson D. Bokhoven V.A. Tao Y. Wilson S. Su L.J. Li Y. Harrison G. Agarwal R. Crawford E.D. Lucia M.S. Pollak M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate 2010 70 8 848 855 10.1002/pros.21118 20127732
    [Google Scholar]
  94. Tamayo C. Diamond S. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Integr. Cancer Ther. 2007 6 2 146 157 10.1177/1534735407301942 17548793
    [Google Scholar]
  95. Hackett E.S. Mama K.R. Twedt D.C. Gustafson D.L. Pharmacokinetics and safety of silibinin in horses. Am. J. Vet. Res. 2013 74 10 1327 1332 10.2460/ajvr.74.10.1327 24066917
    [Google Scholar]
  96. Wu J.W. Lin L.C. Tsai T.H. Drug–drug interactions of silymarin on the perspective of pharmacokinetics. J. Ethnopharmacol. 2009 121 2 185 193 10.1016/j.jep.2008.10.036 19041708
    [Google Scholar]
  97. Fenclova M. Novakova A. Viktorova J. Jonatova P. Dzuman Z. Ruml T. Kren V. Hajslova J. Vitek L. Stranska-Zachariasova M. Poor chemical and microbiological quality of the commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non-reproducible clinical outcomes. Sci. Rep. 2019 9 1 11118 10.1038/s41598‑019‑47250‑0 31366891
    [Google Scholar]
  98. Brantley S.J. Graf T.N. Oberlies N.H. Paine M.F. A systematic approach to evaluate herb-drug interaction mechanisms: Investigation of milk thistle extracts and eight isolated constituents as CYP3A inhibitors. Drug Metab. Dispos. 2013 41 9 1662 1670 10.1124/dmd.113.052563 23801821
    [Google Scholar]
  99. Zi X. Zhang J. Agarwal R. Pollak M. Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells. Cancer Res. 2000 60 20 5617 5620 11059749
    [Google Scholar]
  100. Pickova D. Ostry V. Toman J. Malir F. Presence of mycotoxins in milk thistle (Silybum marianum) food supplements: A review. Toxins 2020 12 12 782 10.3390/toxins12120782 33302488
    [Google Scholar]
  101. Chen P.N. Hsieh Y.S. Chiou H.L. Chu S.C. Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways. Chem. Biol. Interact. 2005 156 2-3 141 150 10.1016/j.cbi.2005.08.005 16169542
    [Google Scholar]
  102. Kawaguchi-Suzuki M. Frye R.F. Zhu H.J. Brinda B.J. Chavin K.D. Bernstein H.J. Markowitz J.S. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab. Dispos. 2014 42 10 1611 1616 10.1124/dmd.114.057232 25028567
    [Google Scholar]
  103. Ramasamy K. Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett. 2008 269 2 352 362 10.1016/j.canlet.2008.03.053 18472213
    [Google Scholar]
  104. Wang H. Tsung A. Mishra L. Huang H. Regulatory T cell: A double-edged sword from metabolic-dysfunction-associated steatohepatitis to hepatocellular carcinoma. EBioMedicine 2024 101 105031 10.1016/j.ebiom.2024.105031 38401419
    [Google Scholar]
  105. Emadi S.A. Rahbardar G.M. Mehri S. Hosseinzadeh H. A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents. Iran. J. Basic Med. Sci. 2022 25 10 1166 1176 36311193
    [Google Scholar]
  106. 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 10.3390/medicina54010001
    [Google Scholar]
  107. Chen L. Wu T. Fan R. Qian Y.S. Liu J.F. Bai J. Zheng B. Liu X.L. Zheng D. Du L.T. Jiang G.Q. Wang Y.C. Fan X.T. Deng G.H. Wang C.Y. Shen F. Hu H.P. Zhang Q.Z. Ye Y.N. Zhang J. Gao Y.H. Xia J. Yan H.D. Liang M.F. Yu Y.L. Sun F.M. Gao Y.J. Sun J. Zhong C.X. Wang Y. Wang H. Kong F. Chen J.M. Wen H. Wu B.M. Wang C.X. Wu L. Hou J.L. Wang H.Y. Cell-free DNA testing for early hepatocellular carcinoma surveillance. EBioMedicine 2024 100 104962 10.1016/j.ebiom.2023.104962 38184937
    [Google Scholar]
  108. Jiang F. Zhao J. Sun J. Chen W. Zhao Y. Zhou S. Yuan S. Timofeeva M. Law P.J. Larsson S.C. Chen D. Houlston R.S. Dunlop M.G. Theodoratou E. Li X. Impact of ambient air pollution on colorectal cancer risk and survival: Insights from a prospective cohort and epigenetic Mendelian randomization study. EBioMedicine 2024 103 105126 10.1016/j.ebiom.2024.105126 38631091
    [Google Scholar]
  109. Mayer K.É. Myers R.P. Lee S.S. Silymarin treatment of viral hepatitis: A systematic review. J. Viral Hepat. 2005 12 6 559 567 10.1111/j.1365‑2893.2005.00636.x 16255756
    [Google Scholar]
  110. Papadimitriou N. Qu C. Harrison T.A. Bever A.M. Martin R.M. Tsilidis K.K. Newcomb P.A. Thibodeau S.N. Newton C.C. Um C.Y. Obón-Santacana M. Moreno V. Brenner H. Mandic M. Chang-Claude J. Hoffmeister M. Pellatt A.J. Schoen R.E. Harlid S. Ogino S. Ugai T. Buchanan D.D. Lynch B.M. Gruber S.B. Cao Y. Hsu L. Huyghe J.R. Lin Y. Steinfelder R.S. Sun W. Guelpen V.B. Zaidi S.H. Toland A.E. Berndt S.I. Huang W.Y. Aglago E.K. Drew D.A. French A.J. Georgeson P. Giannakis M. Hullar M. Nowak J.A. Thomas C.E. Marchand L.L. Cheng I. Gallinger S. Jenkins M.A. Gunter M.J. Campbell P.T. Peters U. Song M. Phipps A.I. Murphy N. Body size and risk of colorectal cancer molecular defined subtypes and pathways: Mendelian randomization analyses. EBioMedicine 2024 101 105010 10.1016/j.ebiom.2024.105010 38350331
    [Google Scholar]
  111. Liu S. Lan B. Wang Y. Yang T. Li L. Ge H. Zeng C. Xu B. Qian H. Ma F. Pyrotinib and trastuzumab combination treatment synergistically overcomes HER2 dependency in HER2-positive breast cancer: Insights from the PHILA trial. EBioMedicine 2024 109 105379 10.1016/j.ebiom.2024.105379 39368454
    [Google Scholar]
  112. Bjørnstad O.V. Carrasco M. Finne K. Ardawatia V. Winge I. Askeland C. Arnes J.B. Knutsvik G. Kleftogiannis D. Paulo J.A. Akslen L.A. Vethe H. Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model. EBioMedicine 2024 108 105325 10.1016/j.ebiom.2024.105325 39232464
    [Google Scholar]
  113. Desai T.A. Hedman Å.K. Dimitriou M. Koprulu M. Figiel S. Yin W. Johansson M. Watts E.L. Atkins J.R. Sokolov A.V. Schiöth H.B. Gunter M.J. Tsilidis K.K. Martin R.M. Pietzner M. Langenberg C. Mills I.G. Lamb A.D. Mälarstig A. Key T.J. Travis R.C. Smith-Byrne K. Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics. EBioMedicine 2024 105 105168 10.1016/j.ebiom.2024.105168 38878676
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673371391250415105506
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Milk Thistle (Silybum marianum): Potential Role in Cancer Prevention
Bentham Science Publishers ; https://doi.org/10.2174/0109298673371391250415105506
/content/journals/cmc/10.2174/0109298673371391250415105506
/content/journals/cmc/10.2174/0109298673371391250415105506
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  • Article Type:     Review Article
Keywords: tumour cell growth ; apoptosis ; Milk thistle ; cellular signalling pathways ; angiogenesis ; metastasis

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