Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The results demonstrate that the elevating ROS can up-regulate the expression of DR5, resulting in apoptosis via mitochondrial pathway. Although the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway served an important role in protecting gastric cancer cells against the injury of ROS, it can’t reverse LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d induced apoptosis via DR5-mediated mitochondrial apoptotic pathway in gastric cancer cells. LCT-3d could be a novel lead compound for development of anti-cancer activity in gastric cancer.
Nitric oxide (NO) modulates plant response by post-translationally modifying proteins, mainly through S-nitrosylation. Ascorbate peroxidase (APX) in the ascorbate-glutathione (AsA-GSH) cycle participates in the removal of hydrogen peroxide (H2O2). However, the relationship between S-nitrosylation and the role of tomato APX (SlAPX) under nitrate stress is still unclear. In this study, the enzyme activity, mRNA expression, and S-nitrosylation level of SlAPX were significantly increased in tomato roots after nitrate treatment. SlAPX protein could be S-nitrosylated by S-nitrosoglutathione in vitro, and APX activity was significantly increased after S-nitrosylation. The SlAPX overexpressed tobacco plants grew better than the wild type (WT) plants under nitrate stress. Meanwhile, the transgenic plants showed lower reactive oxygen species and malondialdehyde content, higher APX, monodehydroascorbate reductase, glutathione reductase activities, ascorbic acid/dehydroascorbic acid, and reduced glutathione/oxidized glutathione ratio, proline, and soluble sugar contents than those in the WT plants under nitrate treatment. Moreover, overexpressed transgenic seeds showed higher tolerance to methyl viologen induced oxidative stress compared with the WT. The NO accumulation and S-nitrosylation APX level were higher in transgenic plants than in WT plants after nitrate stress treatment. Our results provide novel insights into the mechanism of SlAPX modulation excess nitrate stress tolerance involving the S-nitrosylation modification.
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