Resveratrol exerts an antiproliferative effect in pancreatic cancer cells by inducing mitochondrial-mediated apoptosis

Abstract

Resveratrol, an active natural phytoalexin compound mainly derived from grapes exhibits numerous pharmacological activities including anticancer activity. The current evaluate the anticancer potential of resveratrol against pancreatic cancer cells. Our results demonstrate that resveratrol exhibits significant antiproliferative activity against a panel of pancreatic cancer cell lines. Quantification of apoptotic cells after staining with annexin V and propidium iodide (PI) by flow cytometry revealed a significant number of tumor cells undergo apoptosis at higher doses of resveratrol. Further, confirmation by immunoblotting reveals a significant increase in the cleaved product of PARP1 and caspase-3 with a notable expression of mitochondrial resident protein cytochrome-3 at higher doses of resveratrol. Additionally, we observe a high production of reactive oxygen species (ROS) by conversion of DCFDH2A into green fluorescein color when pancreatic cancer cells were exposed to the dose-dependent concentration of resveratrol. To confirm the mitochondrial-dependent apoptosis, JC-1 staining of pancreatic cells exposed to varying doses of resveratrol reveals a significant population of pancreatic cancer cells was stained with JC-1 dye at higher doses of resveratrol indicating the depolarization of mitochondrial membrane potential was induced in pancreatic cancer cells upon resveratrol treatment to kill cells by mitochondrial-dependent apoptosis. In summary, resveratrol exhibits an antiproliferative effect in pancreatic cells by simultaneously induces ROS production and mitochondrial-dependent apoptosis.