Quercetin inhibits human metastatic ovarian cancer cell growth and modulates components of the intrinsic apoptotic pathway in PA-1 cell line

Ovarian cancer is the leading cause of gynaecology related cancer death worldwide. It is often diagnosed with an advanced stage. Apoptosis is a process of programmed cell death controlled by cell cycle machinery and several signaling pathways. Plant-derived compounds have received an increased interest in the treatment of cancer. Quercetin is a flavonoid present in fruits and vegetables which possess anticancer properties. Several studies have been demonstrated that quercetin induces apoptosis in various cancers. However, the apoptotic role of quercetin in metastatic ovarian cancer has not been extensively studied. In the present study, we investigated the apoptotic effect of quercetin on human metastatic ovarian cancer PA-1 cell line. Quercetin treatment (0-200 mu M) for 24h decreases PA-1 cells viability in a dose-dependent manner. The effective dose was identified as 50 and 75 mu M based on MTT assay. Quercetin induces apoptosis in metastatic ovarian cancer cells which were confirmed by AO/EtBr dual staining, DAPI staining and DNA fragmentation assay. Molecules involved in the intrinsic apoptotic pathway were altered by quercetin. Interestingly, antiapoptotic molecules such as Bcl-2, Bcl-xL were decreased while proapoptotic molecules such as caspase-3, caspase-9, Bid, Bad, Bax and cytochrome c were increased in the quercetin-treated PA-1 cells. Our results indicate that quercetin induces mitochondrial-mediated apoptotic pathway and thus it inhibits the growth of metastatic ovarian cancer cells.