Phytochemical analysis and molecular mechanisms of anticancer activity of Stevia rebaudiana extract in gastric cancer cells: In silico docking and functional assays on apoptosis and cell migration

Abstract

Gastric carcinoma (GC) continues to be a substantial worldwide health problem, requiring the investigation of new treatment approaches. Early GC, which can be multifocal and portend a worse prognosis, is classified into four types: Type-I (protruding), Type-II (superficial), Type-III (excavating), and Type-IV (infiltrating with lateral spreading). This research aimed to explore the possible anti-cancer properties of Stevia rebaudiana ethanol extract (EESR) on SGC-7901 GC cells. We conducted a thorough evaluation of the cytotoxic, anti-proliferative, anti-migratory, and pro-apoptotic effects of EESR, as well as its capacity to regulate the PI3K/AKT/mTOR signaling pathway. We used a range of assays, including 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium-bromide (MTT), clonogenic, Transwell chambers, Annexin-V, Western blotting, and molecular docking analysis, to investigate and understand the molecular pathways responsible for the bioactivity of EESR. The findings of our study showed that the viability of cells, capacity to form colonies, ability to migrate, and ability to invade were reduced in a manner that depended on the concentration of EESR. This decrease was accompanied by the initiation of apoptosis and the suppression of the PI3K/AKT/mTOR signaling pathway. The results showed statistically significant findings, with a substantial decrease (∗∗p < 0.01) in colony formation and migration, as well as an increase in apoptotic cells (∗∗p < 0.01) after EESR treatment. Additional molecular docking studies demonstrated substantial interactions between Stevioside, a crucial component of EESR, and the PI3K-mTOR protein complex. These noteworthy results demonstrate the potential of EESR as a natural therapeutic agent for GC. Further study is needed to determine its effectiveness for clinical use.