Raja Singh Paulraj, Sugantha Priya Elayapillai, Balakrishnan Solaimuthu, Arunkumar Ramachandran, Sharmila Govindaraj, Rajalakshmi Manikkam, Arunakaran Jagadeesan
Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
PG & Research Department of Biotechnology & Bioinformatics, Holy Cross College, Tiruchirapalli, 620 002, India.
Mol Cell Biochem. 2017 Mar;427(1-2):69-79. doi: 10.1007/s11010-016-2898-4. Epub 2016 Dec 26.
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.
前列腺癌是全球男性中最常见的恶性肿瘤。PI3K-Akt信号通路似乎对前列腺癌细胞的增殖和存活至关重要。我们早期的研究表明，印楝素（2 µM）通过PI3K/Akt经IGF信号通路阻止细胞存活，并诱导PC-3细胞系凋亡。Akt介导mTOR的磷酸化和激活，mTOR在蛋白质翻译与合成、血管生成以及细胞周期进程的调控中起关键作用。本研究旨在通过蛋白质印迹分析研究印楝素对tPI3K、tAkt、pAkt、tmTOR、GSK3β、pGSK3β、PCNA、c-Myc、细胞周期蛋白D1和生存素蛋白水平的影响。通过吖啶橙/溴化乙锭双重染色（20×）观察细胞凋亡情况，并通过免疫细胞化学检测PCNA的蛋白表达。进行分子对接以了解印楝素与Akt、PCNA和细胞周期蛋白D1之间可能的相互作用。印楝素改变了PI3K-Akt介导的细胞存活和增殖分子。因此，印楝素通过作用于PC-3细胞中的PI3K-Akt-mTOR信号通路在体外发挥抗癌作用。从而，它可作为一种有效的前列腺癌抗癌药物。
