title: Anti-proliferative and apoptosis inducing effect of nimbolide by altering molecules involved in apoptosis and IGF signalling via PI3K/Akt in prostate cancer (PC-3) cell line.
abstract: Prostate cancer is responsible for major deaths globally after lung cancer. Nimbolide is an important constituent of neem, and it acts as a potent inhibitor for many cancer cells. The present study was designed to evaluate the effects of nimbolide on apoptosis and insulin-like growth factor (IGF) signalling molecules in androgen-independent prostate cancer (PC-3) cells line. Nimbolide (0.5-2 μM) treatment resulted in 50% inhibition at a dose of 2 μM in the PC-3 cell line. The mRNA expression of Fas ligand, Fas-associated death domain receptor (FADDR), Bcl-2-associated X protein (Bax), Bcl-2-associated death promoter (Bad), phosphatidylinositide 3-kinases (PI3K), Akt, IGF1, IGF1 receptor (IGF1R) and IGF binding protein 3 were quantified by reverse transcription polymerase chain reaction and protein expression of Bax, cytochrome c, X-linked inhibitor of apoptosis protein (XIAP), B-Cell Lymphoma 2 (Bcl-2), caspases -8, -9, -10 and -3, poly(ADP-ribose) polymerase (PARP), cleaved PARP, IGF1R, PI3K, Akt, p-Akt was determined by western blot analysis, in nimbolide-treated PC-3 cell line. Nimbolide-induced apoptosis by activating DNA fragmentation in PC-3 cells. Nimbolide treatment increased the mRNA of Fas ligand, FADDR, Bax, Bad and IGF binding protein 3, decreased PI3K, Akt, IGF1 and IGF1R, increased protein expression of caspases 8, 3, 10, 9, Bax and cytochrome c and decreased the expression of XIAP, Bcl2, cleaved PARP, p-Akt and IGF1R. The results suggest that nimbolide acts as a potent anti-cancer agent by inducing apoptosis and inhibiting cell proliferation via PI3K/Akt pathway in PC-3 cells.
authors: Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamilnadu, India.
authors: Paulraj
authors: P
authors: Raja Singh
authors: Ramachandran
authors: R
authors: Arunkumar
authors: Velayutham
authors: V
authors: Sivakamasundari
authors: Govindaraj
authors: G
authors: Sharmila
authors: Perumal
authors: P
authors: Elumalai
authors: Elayapillai
authors: E
authors: Suganthapriya
authors: Amalanathan
authors: A
authors: Brindha Mercy
authors: Kalimuthu
authors: K
authors: Senthilkumar
authors: Jegadeesan
authors: J
authors: Arunakaran
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036701:Limonins / Q000494:pharmacology*; D008297:Male; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D036701:Limonins; D013002:Somatomedins; C042198:nimbolide; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt
keywords: PI3K/Akt; apoptosis; nimbolide; prostate cancer