Induction of apoptosis and autophagy via sirtuin1-mediated pathways by momordica charantia in gastric cancer cells

[[abstract]]Sirtuin1 (SIRT1), one of the sirtuin family of proteins, was known to regulate cellular stress response and cell survival through deacetylation of its target proteins and modulation of apoptosis and autophagy. This study aimed to investigate the effects of Momordica charantia (MC) on apoptosis and autophagy and the underlying mechanisms which SIRT1 is involved in gastric cancer (GC) AGS and SC-M1 cells. MC extract (MCE) had potent apoptotic and autophagic effects in both GC cells. The MCE-induced inhibition of p38 mitogen-activated protein kinase and activation of 5'-AMP-dependent kinase (AMPK) lead to the pro-autophagic activity in cells. MCE-induced autophagy was found by the expression of autophagy-related proteins, LC3-II and p62. SIRT1 was significantly downregulated by MCE. The enhanced cell death by SIRT1 activator, SRT1720, indicated the regulatory role of SIRT1 on MCE-mediated cell death in GC cells. The pretreatment of z-VAD-FMK indicated that apoptosis induced by MCE in both GC cells was caspase-independent. Additionally, MCE-inhibited cell proliferation was confirmed by a zebrafish xenograft model, hence, implying the potential of MC for anticancer drug development