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Pak2 inhibition promotes resveratrol‐mediated glioblastoma A172 cell apoptosis via modulating the AMPK‐YAP signaling pathway
Author(s) -
Xing Jin,
Wang Zhihan,
Xu Hao,
Liu Chaobo,
Wei Zilong,
Zhao Liang,
Ren Li
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29515
Subject(s) - ampk , resveratrol , apoptosis , chemistry , signal transduction , microbiology and biotechnology , reactive oxygen species , viability assay , phosphorylation , amp activated protein kinase , cancer research , protein kinase a , biology , biochemistry
As a polyphenolic compound, resveratrol (Res) is widely present in a variety of plants. Previous studies have shown that Res can inhibit various tumors. However, its role in c remains largely unexplored. In the present study, we first demonstrated that Res inhibited cell viability and induced apoptosis of glioblastoma A172 cell. Further experiments showed that Res induced mitochondrial dysfunction and activated the activity of caspase‐9. Functional studies have found that Res treatment is associated with an increase in the expression of Pak2. Interestingly, inhibition of Pak2 could further augment the proapoptotic effect of Res. Mechanistically, Pak2 inhibition induced reactive oxygen species overproduction, mitochondria‐JNK pathway activation, and AMPK‐YAP axis suppression. However, overexpression of YAP could abolish the anticancer effects of Res and Pak2 inhibition, suggesting a necessary role played by the AMPK‐YAP pathway in regulating cancer‐suppressive actions of Res and Pak2 inhibition. Altogether, our results indicated that Res in combination with Pak2 inhibition could further enhance the anticancer property of Res and this effect is mediated via the AMPK‐YAP pathway.