Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC₅₀) of 1.45 μM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD₅₀ (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.

Cancer is a significant health burden in the world. Natural product drugs have received widespread attention because of their safety and effectiveness, stable effects and fewer side effects. Some studies have demonstrated that exopolysaccharide (EPS) from lactic acid bacteria (LAB) can inhibit the growth of many types of cancer cells. In this work, the effects of the EPS from Lactiplantibacillus plantarum YT013 on gastric cancer cells were investigated. Its cytotoxicity was evaluated by MTT assay; at the concentration of 1000 μg/mL, the most significant inhibitory effect occurred in AGS cells, followed by SGC-7901, PANC-1 and HCT116, and less inhibited in HepG2 cells. Cell cycle results showed that EPS prevented AGS cells from transitioning from the S phase to the G₂/M phase. In addition, the results of flow cytometry showed that EPS promoted apoptosis in a concentration-dependent manner. Western blotting also indicated that EPS might lead to apoptosis via the endogenous mitochondrial apoptotic pathway. The safety of lyophilized powder, cell-free culture supernatant and EPS from Lactiplantibacillus plantarum YT013 were evaluated by observing tissue organs through H&E staining, and the results showed that the components were safe and effective and could provide a basis for the development of natural anticancer active drugs.