ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
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.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 95 citations in OpenAlex.
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- Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients.Journal of clinical medicine · 2020Article
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- Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review.International journal of molecular sciences · 2018Review
- Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway.Mediators of inflammation · 2018Article
- Evaluation of Silibinin Effects on the Viability of HepG2 (Human hepatocellular liver carcinoma) and HUVEC (Human Umbilical Vein Endothelial) Cell Lines.Iranian journal of pharmaceutical research : IJPR · 2018Article
- STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer.Oncotarget · 2017Article
- Silibinin attenuates radiation-induced intestinal fibrosis and reverses epithelial-to-mesenchymal transition.Oncotarget · 2017Article
- Silibinin inhibits hypoxia-induced HIF-1α-mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics.Molecular carcinogenesis · 2017Article
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- Silibinin Preferentially Radiosensitizes Prostate Cancer by Inhibiting DNA Repair Signaling.Molecular cancer therapeutics · 2015Article
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Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeSilibinin 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. EXPERIMENTAL
designAthymic 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.
resultsSilibinin 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 decreased c-Jun NH(2)-terminal kinase 1/2 and p38 mitogen-activated protein kinase phosphorylation. A moderate decrease in phosphorylated and total levels of Akt was also noted. A marked inhibitory effect of silibinin on signal transducers and activators of transcription (STAT) 1 (Tyr(701)), STAT1 (Ser(727)), STAT3 (Tyr(705)), STAT3 (Ser(727)), and STAT5 (Tyr(794)) phosphorylation together with a decrease in their total levels was also observed.
conclusionsThese findings provide evidence for antitumor efficacy of silibinin against orthotopically growing prostate tumor in mice with multitargeted mechanistic insights and support its clinical investigation in prostate cancer.
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