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.

Natural products play an important role in drug development and lead compound synthesis. Neocryptolepine is a polycyclic quinoline compound isolated from Cryptolepis sanguinolent. The cytotoxicity of neocryptolepine to gastric cancer cells AGS, MKN45, HGC27, and SGC7901 was not very strong, and it also had certain toxicity to gastric mucosa cells GES-1. Therefore, a series of neocryptolepine derivatives were synthesized by the modification of the structure of neocryptolepine, and their cytotoxicity was evaluated. The results showed that compounds C5 and C8 exhibited strong cytotoxicity to AGS cells. The cell colony formation and cell migration experiments suggested that compounds C5 and C8 could inhibit the proliferation and cell migration of AGS and HGC27 cells. Cell cycle and apoptosis experiments showed that compounds C5 and C8 did not cause the apoptosis of AGS and HGC27 cells but, mainly, caused cell necrosis. Compound C5 had no significant effect on AGS and HGC27 cell cycles at low concentration. After treatment with AGS cells for 24 h at high concentration, compound C5 could significantly arrest the AGS cell cycle in the G2/M phase. Compound C8 had no significant effect on the AGS and HGC27 cell cycles. The results of molecular docking and Western blot showed that compounds C5 and C8 might induce cytotoxicity through the PI3K/AKT signaling pathway. Therefore, compounds C5 and C8 may be promising lead compounds for the treatment of gastric cancer.