Neferine induces cell growth inhibition and apoptosis via ROS-mediated activation of p38 in pancreatic ductal adenocarcinoma cells

Abstract

Pancreatic cancer is a lethal malignancy with limited effective treatment options available. Neferine, an alkaloid derived from the seed embryos of lotus, has been reported to exert tumor suppressive functions in multiple cancer types, but its exact roles in pancreatic ductal adenocarcinoma (PDAC) and the underlying mechanisms remain largely elusive. In this study, cell counting kit-8, clone formation, 5-ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End Labeling staining, and flow cytometry assays were employed to evaluate the anti-tumor effect of neferine against PDAC. Western blotting was performed to analyze the related protein expression. We demonstrated that neferine reduced cellular proliferation and triggered mitochondrial-dependent apoptosis in PDAC cells. Meanwhile, neferine treatment induced the generation of reactive oxygen species (ROS) and p38 activation. Notably, the inhibition of ROS generation and p-p38 expression attenuated the anticancer effects of neferine. In conclusion, ROS-induced p38 activation contributes to the cell growth inhibition of neferine in PDAC cells.