Parthenolide inhibits tumor-promoting effects of nicotine in lung cancer by inducing P53 - dependent apoptosis and inhibiting VEGF expression

In this study, we tested the ability of parthenolide to inhibit the proliferating effect of nicotine in lung cancer cell lines. MTT assay was used to measure cell survival of A549 and H526 cells treated with nicotine, parthenolide, and their combination. Angiogenesis inhibition was measured using VEGF detection kit and apoptosis induction was evaluated by measuring caspase-3 activity. Real time PCR assay was used to detect the change in expression of several genes associated with cell proliferation and apoptosis (CASP3, CASP7, CASP8, CASP9, P53, GADD45, BAX, BIM, Bcl-2, TOPO I, and TOPO II). Parthenolide inhibited lung cancer cells in a concentration-dependent manner and decreased the proliferation stimulating effect of nicotine. Caspase-3 activity and VEGF assays evidenced an apoptosis-inducing and VEGF- inhibiting effects of parthenolide. The real time PCR assay demonstrated that parthenolide down-regulated the expression of Bcl-2 and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which indicates an activation of P53- dependent apoptosis pathway in response to parthenolide. Furthermore, this pathway remained active in the presence of nicotine suggesting the ability of parthenolide to exclude the anti-apoptotic effect of nicotine. Our results indicate that parthenolide inhibits nicotine proliferating effect on lung cancer. The anticancer effect of parthenolide is mediated by angiogenesis inhibition and activation of P53- dependent apoptosis. Pa...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research