Epidermal growth factor-induced prostate cancer (PC3) cell survival and proliferation is inhibited by quercetin, a plant flavonoid through apoptotic machinery

Abstract

Epidermal growth factor (EGF) plays a key role in epithelial malignancies by enhancing cancer cell proliferation, survival, invasion, and metastasis. The aberrant expression of epidermal growth factor receptor (EGFR) by tumors typically confers a more aggressive phenotype and is often predictive of poor prognosis. Quercetin is an anti-oxidative flavonoid widely distributed in fruits and vegetables and have attracted much attention as potential anti-carcinogens. Prostate cancer is the most common cause of cancer related deaths in men. In the present study, we examined the effects of quercetin on EGF induced signaling molecules involved in proliferation, survival and apoptosis in PC-3 cells. EGF-stimulated EGFR, Akt, PI3 K, PDK1 and ERK1/2 protein levels were inhibited by quercetin. The inhibitory effects of quercetin on EGF induced signaling were compared with PI3 K inhibitor (LY294002) and MAPK inhibitor (PD98059). Quercetin down-regulated EGF induced Bcl-2 expression and upregulated Bax protein levels. Caspase-3 activity was significantly increased by quercetin treatment. Acridine orange and ethidium bromide staining showed that quercetin was able to induce apoptosis even in the presence of EGF. To conclude, the present study showed that quercetin inhibits EGF induced cell survival, proliferation and induced apoptosis in PC-3 cells.