Inhibition of cancer cell growth in gemcitabine-resistant pancreatic carcinoma by mangiferin phytochemical involves induction of autophagy, endogenous ROS production, cell cycle disruption, mitochondrial mediated apoptosis and suppression of cancer cell migration and invasion.

Abstract

Purpose: Pancreatic cancer causes considerable mortality across the globe and the treatment options for pancreatic cancer are limited. Besides, the development of drug resistance among the pancreatic cancer cells makes it even difficult to manage. In this study the anticancer effects of mangiferin were examined against the Mia-PaCa2 gemcitabine-resistant pancreatic cancer cells.

Materials/methods: Cell proliferation was examined by MTT assay while as apoptosis was detected by fluorescent microscopy and western blot. Effects on cell cycle, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. The fact that mangiferin induced autophagy was demonstrated by fluorescent microscopy in combination with western blot method.

Results: The results revealed that mangiferin inhibited the growth of the Mia-PaCa2 cells and exhibited an IC50 of 10 µM. Nonetheless, the toxic effects of mangiferin were less on the normal cells. Mangiferin induces apoptosis in the Mia-PaCa2 cells which was associated with enhancement of Bax/Bcl-2 ratio. Further investigations revealed that mangiferin triggered autophagy in the Mia-PaCa2 cells as evident from the elevated expressions of the LC3 II and Beclin-1. The antiproliferative effects of mangiferin were also accompanied by the generation of endogenous ROS and cell cycle arrest. Investigation of the effects of mangiferin on the invasion and migration of the Mia-PaCa2 cells showed that mangiferin suppressed the migration and invasion potential of the Mia-PaCa2 cells.

Conclusions: These findings suggest that mangiferin could be utilised for the development of chemotherapy for pancreatic cancer provided further in depth experiments are carried out along with its toxicological studies.