Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway

Urolithin A (UA) is a microbial metabolite of natural polyphenols ellagitannins and ellagic acid with well-established antitumor properties against various malignancies. However, the exact role of UA in gastric cancer (GC) progression remains largely unclear. In the present study, we investigated the effects and potential mechanisms of UA in GC in vitro and in vivo. Our results revealed that UA could suppress GC cell proliferation, inhibit migration and invasion, promote apoptosis, and induce autophagy via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway in vitro. The autophagy inhibitors 3-methyladenine and chloroquine augmented the inhibitory effect of UA on proliferation and promoted apoptosis, implying that UA mediated the cytoprotective role of autophagy. Meanwhile, the in vivo experiments showed that UA effectively suppressed tumor growth, enhanced the therapeutic effects, and alleviated chemotherapy toxicity in xenograft models. Overall, these findings offer novel insights into the role of UA in tumor therapy and suggest that UA may possess potential therapeutic applications for GC.