MYRICETIN INDUCES APOPTOSIS VIA CASPASE ACTIVATION AND INHIBITION OF PI-3 KINASE/AKT AND ERK PATHWAYS IN HUMAN PANCREATIC CELLS

Abstract

Myricetin a polyphenolic flavonoid is present in fruits and vegetables. Studies have suggested that various flavonoids also induce cell death in cancer cells and may influence various intracellular signaling pathways, including Mitogen-Activated Protein Kinases (MAPKs) and PI-3 kinases. In this study, we evaluated the effect of myricetin on the viability and apoptosis in pancreatic cancer cells, and evaluated its effect on PI-3K signaling pathways, which leads to cell proliferation, migration, and apoptosis. Methods: Pancreatic cancer cells (MiaPaCa-2/PANC-1, S2013, and S2VP10) and normal pancreatic ductal cells were treated with myricetin 25-200 μM. Cell viability was evaluated by CCK-8. The parameters of apoptosis, Annexin V and Caspase 3/9 activation were measured by flow cytometry and luminescence-based caspase assay, respectively. The effect on the activation of Akt, MAPK, and p38 was measured by evaluating the level of the active phosphorilated form of these enzymes by western blotting. Results: Myricetin reduced the viability of pancreatic cancer cell lines in a dose-dependent and time-dependent fashion without affecting the viability of normal pancreatic ductal cells. Myricetin induces apoptosis in pancreatic cancer cells, as suggested by increased annexin V staining and activation of caspase 3/9. Myricetin reduced the levels of phosphorilated p-Akt, p-MAPK, and p-P38 as measured by western blot, which suggests their inactivation. Conclusion: Myricetin induces apoptotic cell death in pancreatic cancer cells without influencing the viability of normal ductal cells. It is a potential therapeutic candidate for treating pancreatic cancer.