Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 69, Issue 29, Pages 8130-8143Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c02620
Keywords
isorhamnetin; apoptosis; autophagy; PI3K; gastric cancer
Funding
- National Natural Science Foundation of China [81960869]
- Provincial University Industry Support Project in Gansu [2020C-15]
- Provincial Key Talent Project [GZT2020-9-1]
- Basic Research Innovation Group in Gansu [20JR10RA332]
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Isorhamnetin (ISO), a chemical substance derived from plants, has been found to have antitumor effects. In a hypoxic environment, ISO can significantly inhibit gastric cancer cell autophagy by targeting PI3K and blocking the PI3K-AKT-mTOR signaling pathway, as well as promote cell apoptosis, making it a promising candidate for the treatment of gastric cancer.
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.
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