title: Inhibition of cell survival and proliferation by nimbolide in human androgen-independent prostate cancer (PC-3) cells: involvement of the PI3K/Akt pathway.
abstract: 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.
authors.affiliation: Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
authors.forename: Paulraj
authors.initials: P
authors.lastname: Raja Singh
authors.affiliation: Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
authors.forename: Elayapillai
authors.initials: E
authors.lastname: Sugantha Priya
authors.affiliation: Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
authors.forename: Solaimuthu
authors.initials: S
authors.lastname: Balakrishnan
authors.affiliation: Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Arunkumar
authors.affiliation: Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
authors.forename: Govindaraj
authors.initials: G
authors.lastname: Sharmila
authors.affiliation: PG & Research Department of Biotechnology & Bioinformatics, Holy Cross College, Tiruchirapalli, 620 002, India.
authors.forename: Manikkam
authors.initials: M
authors.lastname: Rajalakshmi
authors.affiliation: Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India. j_arunakaran@hotmail.com.
authors.forename: Jagadeesan
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D036701:Limonins / Q000494:pharmacology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D036701:Limonins; C042198:nimbolide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell survival; Docking; Nimbolide; Proliferation; Prostate cancer