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• W237016095 abstract "Introduction: Anti-oxidative extracts from the milk thistle plant (Silybum marianum) have been shown to have anti-proliferative effects in several tumor types. Silibinin is the primary active component isolated from the crude seed extract, silymarin. It has been used as a dietary supplement for hepatoprotection for over 2000 years. Silibinin has been shown to be safe in multiple animal models and has had no significant adverse events in human studies. We investigated the potential for this non-toxic flavolignan to inhibit proliferation of three well-characterized human colon cancer cells lines: Fet, Geo, HCT116. Methods: The MTT cell-viability assay was performed to study the effect of silibinin on proliferation. FACS analysis was used to determine the effects of silibinin on cell cycle. PARP cleavage and expression levels of p21, p27, cyclins B1/D1, and CDK-2 were measured. COX-2 levels were also measured. The experiments were performed in triplicate and reported as mean values with standard errors. The data was analyzed using Dunnett’s multiple comparison test, and a p-value of <0.05 was considered statistically significant. Results: The MTT assay revealed a strong dose-dependent inhibitory effect. Treatment at 75 micrograms/ml led to 50% inhibition of cell-viability (IC-50) in Fet and Geo lines at 72 hrs. An IC50 dose of 40 ug/ml was obtained in poorly-differentiated HCT116 at 72 hrs. FACS analysis demonstrated statistically significant cell-cycle arrest in all cell lines. G2-M phase arrests in Fet and Geo cell lines (p<0.001) and a G1 arrest in HCT116 (p 0.005) were noted. There was no evidence of apoptosis via PARP cleavage. Cyclin B1/D1 and CDK-2 levels were inhibited. No significant change was noted in expression of cell cycle inhibitors, p21 or p27. There was no effect on COX-2 expression. Conclusions: Silibinin significantly inhibits proliferation through cell-cycle arrest via inhibition of cyclin-CDK promoter activity. Despite its antioxidant profile, there is no effect on COX-2 expression. In contrast to previous studies of other cell lines, apoptosis does not appear to be increased in the human colon cancer cell lines, Fet, Geo, and HCT116. Inhibition of cell cycle regulatory proteins plays a fundamental role in silibinin’s mechanism of action, and this may serve as a tool for synergistic use with conventional chemotherapeutics." @default.
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• W237016095 date "2007-02-01" @default.
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• W237016095 title "46" @default.
• W237016095 doi "https://doi.org/10.1016/j.jss.2006.12.055" @default.
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