Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment
Chenghao Li, Jiawei Li, Yan Li, Ling Li, Ya-Li Luo, Junjie Li, Yiming Zhang, Yanru Wang, Xiuzhu Liu, Xiaotian Zhou, Hongxia Gong, Xiaojie Jin, Yongqi Liu
Abstract
A tumor-related hypoxic microenvironment can promote the proliferation of gastric cancer cells, and hypoxic-induced autophagy is the main mechanism of protection against hypoxia in gastric cancer cells. Isorhamnetin (ISO) is a chemical substance derived from plants, mainly from the sea buckthorn. Previous studies have shown that ISO has antitumor effects, but the effects of ISO against gastric cancer in a hypoxic environment are still unknown. In this study, we investigated the effects of ISO against gastric cancer in a hypoxic environment and the mechanisms underlying ISO-induced gastric cancer cell death. The results show that ISO targeted PI3K and blocked the PI3K-AKT-mTOR signaling pathway, significantly inhibiting gastric cancer cell autophagy in a hypoxic environment, inhibiting cell proliferation, decreasing mitochondrial membrane potential, and promoting mitochondria-mediated apoptosis. ISO, a functional food component, is a promising candidate for the treatment of gastric cancer.