{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:43:46Z","timestamp":1792799026242,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,7]],"date-time":"2024-01-07T00:00:00Z","timestamp":1704585600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Programmed cell death (PCD) induction is a promising strategy for killing gastric cancer cells. In this study, we investigated the effects of chrysophanol on apoptosis and ferroptosis in gastric cancer cells. Chrysophanol in concentrations ranging from 0 to 100\u2009\u03bcM were used to treat GES\u20101, HGC\u201027 and AGS cells. Cell counting kit\u20108 assay, colony formation assay, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine staining, flow cytometry, JC\u20101 probe insertion, dihydroethidium staining and western blotting were performed. The effects of chrysophanol on gastric cancer cells were evaluated in\u00a0vivo using a xenograft mouse model. Chrysophanol had no cytotoxic effects on GES\u20101 cells. Chrysophanol with concentrations higher than 25\u2009\u03bcM inhibited gastric cancer cell colony formation and proliferation. Chrysophanol induces gastric cancer cell apoptosis in a dose\u2010dependent manner, accompanied by mitochondrial membrane potential dysfunction and cytochrome <jats:italic>c<\/jats:italic> release. Additionally, chrysophanol increased the levels of reactive oxygen species, total iron, and Fe<jats:sup>2+<\/jats:sup> in HGC\u201027 and AGS cells, in a dose\u2010dependent manner. Treatment of cells with the ferroptosis inhibitor ferrostatin\u20101 attenuated the effects of chrysophanol on cell survival and the expression of ferroptosis markers SLC7A11 and GPX4. Screening by GEO software indicated that the mTOR signalling pathway is possibly regulated by chrysophanol. Furthermore, mTOR overexpression significantly reversed the inhibitory effects of chrysophanol on gastric cancer cells. In gastric cancer xenograft mouse models, chrysophanol treatment inhibited tumour growth and downregulated SLC7A11 and GPX4. Chrysophanol induces apoptosis and ferroptosis, making it a potential candidate for killing gastric cancer cells. The beneficial effects of chrysophanol may be attribute to the targeted regulation of mTOR.<\/jats:p>","DOI":"10.1111\/cbdd.14417","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T01:19:22Z","timestamp":1704676762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chrysophanol induces apoptosis and ferroptosis of gastric cancer cells by targeted regulation of <scp>mTOR<\/scp>"],"prefix":"10.1111","volume":"103","author":[{"given":"Sujuan","family":"Xi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology PLA Naval Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology PLA Naval Medical Center  Shanghai 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