The curcumin analogue WZ35 affects glycolysis inhibition of gastric cancer cells through ROS-YAP-JNK pathway.

The curcumin analogue WZ35 affects glycolysis inhibition of gastric cancer cells through ROS-YAP-JNK pathway. Food Chem Toxicol. 2020 Jan 17;:111131 Authors: Chen T, Zhao L, Chen S, Zheng B, Chen H, Zeng T, Sun H, Zhong S, Wu W, Lin X, Wang L Abstract To investigate the anti-tumor activities of WZ35 and its possible molecular mechanism, bioinformatics analysis and the hematoxylin-eosin (HE) staining were applied to evaluate the Yes-associated-protein (YAP) level in gastric cancer. Cell counting kit-8 (CCK-8) was used to examine cell viability. Apoptosis was determined by flow cytometry analysis. Seahorse bioenergetics analyzer was used to investigate the alteration of oxygen consumption and aerobic glycolysis rate. SiRNA transfection was applied to silence endogenous YAP. Western blot was performed to detect indicated proteins. We found that treatment of gastric cancer cells with WZ35 exerted stronger anti-tumor activities than curcumin. Mechanistically, our research showed that WZ35 inhibited glycolysis, and induced reactive oxygen species (ROS) generation, resulting in Jun N-terminal Kinase (JNK) activation through downregulation of YAP in gastric cancer cells. ROS mediated YAP downregulation and JNK activation was regulated by glycolysis. Abrogation of ROS production markedly attenuated WZ35 induced anti-tumor activities as well as YAP downregulation and JNK activation. Similarly, the JNK inhibitor significantly reversed WZ35 indu...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research