Heptaphylline inhibits the proliferation and epithelial to mesenchymal transition of human pancreatic cancer cells via induction of apoptosis and autophagy

Abstract

Heptaphylline, a carbazole alkaloid, has been shown to exert anticancer effects against different human cancers. The study was designed to evaluate the anticancer effects of heptaphylline against the human pancreatic cancer cell and to explore the underlying mechanism. The results showed that heptaphylline inhibited the proliferation of all the pancreatic cancer cell lines with lowest IC50 of 12 µM against the PANC1 cells. In contrary, the IC50 of heptaphylline was around eight times higher against the normal H6c7 cells. The transwell assays revealed heptaphylline inhibited the migration and invasion of pancreatic cancer cells in a concentration-dependent manner. Additionally, the epithelial to mesenchymal transition of the PANC1 cells was also inhibited upon treatment with heptaphylline. The antiproliferative effects of heptaphylline were exerted via induction of apoptosis in pancreatic cancer cells. The apoptosis was associated with an increase in Bax, decrease in Bcl-2 expression, discharge of cytochrome c and cleavage of PARP, caspase-3 and caspase-9. AO staining revealed that heptaphylline induced autophagy in PANC1 cancer cells by increasing the expression of LC3B-II and Beclin-1. Taken together, heptaphylline suppresses the growth of pancreatic cancer via induction of apoptosis and autophagy and may prove a potent lead molecule for the development of chemotherapy.