An updated review at molecular pharmacological level for the mechanism of anti-tumor, antioxidant and immunoregulatory action of silibinin

Yaoxue Xuebao

Volumn 45, Issue 4, 2010, Pages 413-421

  Wang, Hong Jun ^a   Jiang, Yuan Yuan ^a   Ping, L U ^a   Wang, Qiong ^a   Ikejima, Takashi ^a  

^a SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Antioxidation; Immunoregulation; Silibinin; Tyrosine kinase

Indexed keywords

AMYLOID BETA PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR; HYDROXYL RADICAL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; SILIBININ; SOMATOMEDIN C RECEPTOR; TYROSINE KINASE RECEPTOR;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; CANCER CELL CULTURE; COGNITIVE DEFECT; DRUG EFFECT; DRUG MECHANISM; DRUG STRUCTURE; ENZYME INHIBITION; IMMUNOREGULATION; INFLAMMATION; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION;

AMYLOID BETA-PEPTIDES; ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; ANTIOXIDANTS; ENZYME ACTIVATION; FREE RADICAL SCAVENGERS; HUMANS; MILK THISTLE; MOLECULAR STRUCTURE; NF-KAPPA B; PROTEIN-TYROSINE KINASES; REACTIVE OXYGEN SPECIES; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, IGF TYPE 1; SIGNAL TRANSDUCTION; SILYMARIN;

EID: 77951601718     PISSN: 05134870     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (51)

1. Li L, Gao Y, Zhang L, et al. Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma [J]. Cancer Lett, 2008, 272: 61-69.
2. Singh RP, Dhanalakshmi S, Mohan S, et al. Silibinin inhibits UVB- and epidermal growth factor-induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-kappaB in mouse epidermal JB6 cells [J]. Mol Cancer Ther, 2006, 5: 1145-1153. (Pubitemid 43881306)
3. Qi L, Singh RP, Lu Y, et al. Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line [J]. Cancer Biol Ther, 2003, 2: 526-531.
4. Provinciali M, Papalini F, Orlando F, et al. Effect of me silybin-phosphatidylcholine complex (IdB 1016) on the development of mammary tumors in HER-2/neu transgenic mice [J]. Cancer Res, 2007, 67: 2022-2029. (Pubitemid 46424219)
5. Tyagi A, Sharma Y, Agarwal C, et al. Silibinin impairs constitutively active TGFalpha-EGFR autocrine loop in advanced human prostate carcinoma cells [J]. Pharm Res, 2008, 25: 2143-2150.
6. Cheung CW, Taylor PJ, Kirkpatrick CM, et al. Therapeutic value of orally administered silibinin in renal cell carcinoma: manipulation of insulin-like growth factor binding protein-3 levels [J]. BJU Int, 2007, 100: 438-444.
7. Raina K, Blouin MJ, Singh RP, et al. Dietary feeding of silibinin inhibits prostate tumor growth and progression in transgenic adenocarcinoma of the mouse prostate model [J]. Cancer Res, 2007, 67: 11083-11091. (Pubitemid 350145939)
8. Verschoyle RD, Greaves P, Patel K, et al. Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels [J]. Eur J Cancer, 2008, 44: 898-906.
9. Wang HJ, Tashiro S, Onodera S, et al. Inhibition of insulin-like growth factor 1 receptor signaling enhanced silibinin-induced activation of death receptor and mitochondrial apoptotic pathways in human breast cancer MCF-7 cells [J]. J Pharmacol Sci, 2008, 107: 260-269. (Pubitemid 352030312)
10. Singh RP, Gu M, Agarwal R. Silibinin inhibits colorectal cancer growth by inhibiting tumor cell proliferation and angiogenesis [J]. Cancer Res, 2008, 68: 2043-2050. (Pubitemid 351416592)
11. Singh RP, Deep G, Blouin MJ, et al. Silibinin suppresses in vivo growth of human prostate carcinoma PC-3 tumor xenograft [J]. Carcinogenesis, 2007, 28: 2567-2574.
12. Yang SH, Lin JK, Huang CJ, et al. Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation [J]. J Surg Res, 2005, 128: 140-146.
13. Agarwal C, Tyagi A, Kaur M, et al. Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells [J]. Carcinogenesis, 2007, 28: 1463-1470. (Pubitemid 47243538)
14. Nomura M, Takahashi T, Nagata N, et al. Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells [J]. Biol Pharm Bull, 2008, 31: 1403-1409. (Pubitemid 351930656)
15. Hsieh YS, Chu SC, Yang SF, et al. Silibinin suppresses human osteosarcoma MG-63 cell invasion by inhibiting the ERK-dependent c-Jun/AP-1 induction of MMP-2 [J]. Carcinogenesis, 2007, 28: 977-987.
16. Gu M, Dhanalakshmi S, Mohan S, et al. Silibinin inhibits ultraviolet B radiation-induced mitogenic and survival signaling, and associated biological responses in SKH-1 mouse skin [J]. Carcinogenesis, 2005, 26: 1404-1413.
17. Singh RP, Dhanalakshmi S, Agarwal C, et al. Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications for angioprevention and antiangiogenic therapy [J]. Oncogene, 2005, 24: 1188-1202.
18. Bheda A, Creek KE, Pirisi L. Loss of p53 induces epidermal growth factor receptor promoter activity in normal human keratinocytes [J]. Oncogene, 2008, 27: 4315-4323. (Pubitemid 352009996)
19. Werner H, Maor S. The insulin-like growth factor 1 receptor gene: a downstream target for oncogene and tumor suppressor action [J]. Trends Endocrinol Metab, 2006, 17: 236-242. (Pubitemid 44080616)
20. Wang HJ, Li D, Yang FY, et al. Oridonin induces human melanoma A375-S2 cell death partially through inhibiting insulin-like growth factor 1 receptor signaling [J]. J Asian Nat Prod Res, 2008, 10: 787-798.
21. Zhou L, Liu P, Chen B, et al. Silibinin restores paclitaxel sensitivity to paclitaxel-resistant human ovarian carcinoma cells [J]. Anticancer Res, 2008, 28: 1119-1127. (Pubitemid 351578963)
22. Jiang YY, Wang HJ, Wang J, et al. The protective effect of silibinin on human melanoma A375-S2 cells against mitomycin c induced intrinsic apoptosis [J]. J Pharmacol Sci, 2009, 111: 137-146.
23. Zhou B, Wu LJ, Li LH, et al. Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1 [J]. J Pharmacol Sci, 2006, 102: 387-395. (Pubitemid 44954598)
24. Khan SA, Ahmad B, Alam T. Synthesis and antihepatotoxic activity of some new chalcones containing 1, 4-dioxane ring system [J]. Pak J Pharm Sci, 2006, 19: 290-294.
25. 2 exposure in erythrocytes [J]. Basic Clin Pharmacol Toxicol, 2007, 100: 414-419.
26. Fu H, Lin M, Muroya Y, et al. Free radical scavenging reactions and antioxidant activities of silybin: mechanistic aspects and pulse radiolytic studies [J]. Free Radic Res, 2009, 43: 887-897.
27. Fu H, Katsumura Y, Lin M, et al. Fast repair activities towards dGMP hydroxyl radical adducts by silybin and its analogues [J]. J Radiat Res, 2008, 49: 609-614.
28. Wang HJ, Jiang YY, Wei XF, et al. Silibinin induces protective superoxide generation in human breast cancer MCF-7 cells [J]. Free Radic Res, 2010, 44: 90-100.
29. Svobodová A, Zdarilová A, Walterová D, et al. Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes [J]. J Dermatol Sci, 2007, 48: 213-224.
30. Dhanalakshmi S, Mallikarjuna GU, Singh RP, et al. Dual efficacy of silibinin in protecting or enhancing ultraviolet B radiation-caused apoptosis in HaCaT human immortalized keratinocytes [J]. Carcinogenesis, 2004, 25: 99-106. (Pubitemid 38128622)
31. Li LH, Wu LJ, Tashiro S, et al. Silibinin prevents UV-induced HaCaT cell apoptosis partly through inhibition of caspase-8 pathway [J]. Biol Pharm Bull, 2006, 29: 1096-1101. (Pubitemid 43845466)
32. Lu P, Mamiya T, Lu L, et al. Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice [J]. Br J Pharmacol, 2009, 157: 1270-1277.
33. Lu P, Mamiya T, Lu L, et al. Silibinin attenuates amyloid {beta}25-35 peptide-induced memory impairments: implication of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-{alpha}) in mice [J]. J Pharmacol Exp Ther, 2009, 331: 319-326.
34. Zhou B, Wu LJ, Tashiro S, et al. Protective effect of silibinin against isoproterenol-induced injury to cardiac myocytes and its mechanism [J]. Acta Pharm Sin, 2007, 42: 263-268.
35. Brandon-Warner E, Sugg JA, Schrum LW, et al. Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma [J]. Cancer Lett, 2010, in press.
36. Das SK, Vasudevan DM. Protective effects of Silymarin, a milk thistle (Silybum marianum) derivative on ethanol-induced oxidative stress in liver [J]. Indian J Biochem Biophys, 2006, 43: 306-311.
37. Ligeret H, Brault A, Vallerand D, et al. Antioxidant and mitochondrial protective effects of silibinin in cold preservation-warm reperfusion liver injury [J]. J Ethnopharmacol, 2008, 115: 507-514. (Pubitemid 350299090)
38. Guigas B, Naboulsi R, Villanueva GR, et al. The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase [J]. Cell Physiol Biochem, 2007, 20: 925-934. (Pubitemid 350059735)
39. Detaille D, Sanchez C, Sanz N, et al. Interrelation between the inhibition of glycolytic flux by silibinin and the lowering of mitochondrial ROS production in perifused rat hepatocytes [J]. Life Sci, 2008, 82: 1070-1076.
40. Wallace S, Vaughn K, Stewart BW, et al. Milk thistle extracts inhibit the oxidation of low-density lipoprotein (LDL) and subsequent scavenger receptor-dependent monocyte adhesion [J]. J Agric Food Chem, 2008, 56: 3966-3972. (Pubitemid 351967934)
41. Tyagi A, Singh RP, Ramasamy K, et al. Growth inhibition and regression of lung tumors by silibinin: modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3 [J]. Cancer Prev Res (Phila Pa), 2009, 2: 74-83.
42. Tai KY, Shieh YS, Lee CS, et al. Ax1 promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1 [J]. Oncogene, 2008, 27: 4044-4055.
43. Schümann J, Prockl J, Kiemer AK, et al. Silibinin protects mice from T cell-dependent liver injury [J]. J Hepatol, 2003, 39: 333-340. (Pubitemid 37070249)
44. Al-Anati L, Essid E, Reinehr R, et al. Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells [J]. Mol Nutr Food Res, 2009, 53: 460-466.
45. Min K, Yoon WK, Kim SK, et al. Immunosuppressive effect of silibinin in experimental autoimmune encephalomyelitis [J]. Arch Pharm Res, 2007, 30: 1265-1272.
46. Lee JS, Kim SG, Kim HK, et al. Silibinin polarizes Th1/Th2 immune responses through the inhibition of immunostimulatory function of dendritic cells [J]. J Cell Physiol, 2007, 210: 385-397.
47. Chittezhath M, Deep G, Singh RP, et al. Silibinin inhibits cytokine-induced signaling cascades and down-regulates inducible nitric oxide synthase in human lung carcinoma A549 cells [J]. Mol Cancer Ther, 2008, 7: 1817-1826.
48. Gu M, Singh RP, Dhanalakshmi S, et al. Silibinin inhibits inflammatory and angiogenic attributes in photocarcinogenesis in SKH-1 hairless mice [J]. Cancer Res, 2007, 67: 3483-3491. (Pubitemid 46724890)
49. Falasca K, Ucciferri C, Mancino P, et al. Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection [J]. J Med Virol, 2008, 80: 1900-1906.
50. Haddad Y, Vallerand D, Brault A, et al. Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis [J]. Evid Based Complement Alternat Med, 2010, in press.
51. Surh YJ. NF-kappa B and Nrf2 as potential chemopreventive targets of some anti-inflammatory and antioxidative phytonutrients with anti-inflammatory and antioxidative activities [J]. Asia Pac J Clin Nutr, 2008, 17 Suppl 1: 269-272.