Silibinin suppresses growth of human prostate carcinoma PC-3 orthotopic xenograft via activation of extracellular signal-regulated kinase 1/2 and inhibition of signal transducers and activators of transcription signaling.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Rana P SinghRajesh Agarwal

Abstract

Silibinin is currently under phase II clinical trial in prostate cancer patients; however, its antitumor effects and mechanisms are not completely understood. Herein, we studied the efficacy and associated mechanisms of silibinin against orthotopically growing advanced human prostate carcinoma PC-3 tumors. Athymic male mice were orthotopically implanted with PC-3 cells in prostate and 1 week later after surgical recovery were gavaged daily with silibinin (100 mg/kg body weight) for 7 weeks. Silibinin treatment reduced the lower urogenital weight (including tumor, prostate, and seminal vesicle) by 40% (P < 0.05) without any toxicity in mice. Silibinin decreased proliferating cell nuclear antigen expression and proliferating cells (P < 0.001) but increased cleaved caspase-3-positive cells (P < 0.01) and apoptotic cells (P < 0.001) and suppressed tumor microvessel density (P < 0.001) and vascular endothelial growth factor expression (P = 0.02). Decreased levels of cyclin-dependent kinases 2, 4, and 6, CDC2, and cyclins D1, D3, E, and A were observed, indicating an inhibitory effect of silibinin on cell cycle progression. Silibinin showed a tremendous increase in extracellular signal-regulated kinase 1/2 phosphorylation but decreas...Continue Reading

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Citations

Aug 18, 2010·Cancer Metastasis Reviews·Gagan Deep, Rajesh Agarwal
Feb 22, 2012·Cancer Metastasis Reviews·Luis A AparicioAngélica Figueroa
May 25, 2013·Nutrition and Cancer·Dhanya Nambiar, Rana P Singh
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