Oleanolic acid induces apoptosis and autophagy via the PI3K/AKT/mTOR pathway in AGS human gastric cancer cells

Abstract

• Oleanolic acid inhibited AGS human gastric cancer cells by inducing apoptosis. • Oleanolic acid induced protective-autophagy in AGS cancer cell. • Oleanolic acid induced apoptosis and autophagy through PI3K/AKT/mTOR pathway. • Oleanolic acid suppress tumor growth by downregulating AKT pathway. Oleanolic acid (OA) is widely distributed in food and medicinal plants, it reportedly exerts anti-inflammatory and anti-cancer effects. In this study, we investigated the effect of OA on human gastric cancer cells AGS in vitro and in vivo. The OA treatment significantly inhibited the AGS cell viability. Apoptosis was confirmed via annexin V/PI staining and 4′,6-diamidino-2-phenylindole (DAPI) staining. The results from western blotting revealed that treatment with OA affected apoptosis-related protein. Meanwhile, OA induced autophagy, characterized by the formation of autophagic vacuoles and acidic vesicular organelles, also increased autophagy-related protein. Inhibition of autophagy further reduced cell proliferation. Moreover, OA treatment decreased phosphorylation of PI3K/AKT/mTOR pathway proteins. Finally, we found that OA reduced tumor volume and weight in xenograft mice via apoptosis without side effects. Overall, our study provides experimental evidence for the anti-cancer action of OA and suggests the possibility of its use as an adjuvant in gastric cancer therapy.