Inhibition of cell survival and proliferation by nimbolide in human androgen-independent prostate cancer (PC-3) cells: involvement of the PI3K/Akt pathway

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• 作者：Paulraj Raja Singh ; Elayapillai Sugantha Priya…
• 关键词：Cell survival ; Docking ; Nimbolide ; Proliferation ; Prostate cancer
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：427
• 期：1-2
• 页码：69-79
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Medical Biochemistry; Oncology; Cardiology;
• 出版者：Springer US
• ISSN：1573-4919
• 卷排序：427

文摘

Prostate cancer is most common malignancy among men in the world. PI3K-Akt signaling appears to be critical to prostate cancer cell proliferation and survival. Our earlier study reveals that nimbolide (2 µM) prevents cell survival via IGF signaling pathway through PI3K/Akt and induces apoptosis in PC-3 cell line. Akt mediates the phosphorylation and activation of mTOR that plays a critical role in the regulation of protein translation and synthesis, angiogenesis, and cell cycle progression. The present study was aimed to investigate the effect of nimbolide on tPI3K, tAkt, pAkt, tmTOR, GSK3β, pGSK3β, PCNA, c-Myc, Cyclin D1, and Survivin protein levels by western blot analysis. Apoptosis was visualized by Ao/EtBr dual staining (20×), and protein expression of PCNA by immunocytochemistry was performed. Molecular docking was performed to understand the possible interaction between nimbolide and Akt, PCNA, and Cyclin D1. Nimbolide altered the PI3K-Akt-mediated cell survival and proliferative molecules. Thus, nimbolide exerted anticancer effects in vitro by representing the PI3K-Akt-mTOR pathway in PC-3 cells. Thereby, it acts as a potent anticancer drug for prostate cancer.