Antitumor Effects of Glychionide-A Flavonoid in Human Pancreatic Carcinoma Cells Are Mediated by Activation of Apoptotic and Autophagic Pathways, Cell Cycle Arrest, and Disruption of Mitochondrial Membrane Potential
Lei Yu, Min Chen, Rui Zhang, Ting Xu
(Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China (mainland))
Med Sci Monit 2019; 25:962-969
Pancreatic cancer has high incidence and low survival rates around the globe, mainly due to late diagnosis and unavailability of efficient chemotherapeutic agents. In the present study, the anticancer potential of glychionide-A was examined against PANC-1 pancreatic cancer cells.
MATERIAL AND METHODS: CellTiter-Glo Luminescent Cell Viability Assay Kits were used for assessment of cell viability. Electron microscopy and DAPI staining were used for the detection of apoptosis and autophagy, respectively. Annexin V/PI staining was used for determination of apoptotic cell percentage. Cell cycle distribution and ROS and MMP levels were determined by flow cytometry. Protein expression was examined by Western blot analysis.
RESULTS: The results revealed that glychionide-A significantly inhibited the proliferation of the PANC-1 pancreatic cancer cells (IC₅₀, 14 µM). However, minimal toxicity was observed against the normal hTRET-HPNE pancreatic cells (IC₅₀ 100 µM). The anticancer activity of glychionide-A against the PANC-1 cells was found to be due to induction of autophagy and apoptosis. Glychionide-A prompted apoptosis and autophagy and was also associated with alteration in apoptosis- (Bax, Caspase 9 and Bcl-2) and autophagy- (LC3I, II, Beclin 1 and p62) related protein expression. Glychionide-A also caused the arrest of PANC-1 cells in the G2/M phase of the cell cycle. The percentage of PANC-1 cells in G₂ phase increased from 19.5% to 49.4% upon treatment with glychionide-A. Finally, glychionide-A caused an increase in the level of ROS and decline in MMP levels of the PANC-1 pancreatic cancer cells.
CONCLUSIONS: In brief, these results reveal that glychionide-A significantly inhibits the growth of pancreatic cancer cells via inducing apoptosis and autophagy, and could prove valuable in the chemotherapeutic treatment of pancreatic cancer. Therefore, further research is needed, especially more advanced in vivo experiments.
Keywords: Apoptosis, Autophagy, Cell Cycle, Pancreatic Neoplasms