Novel β-phenylacrylic acid derivatives exert anti-cancer activity by inducing Src-mediated apoptosis in wild-type KRAS colon cancer.

ABSTRACT: Many stress conditions including chemotherapy treatment is known to activate Src and under certain condition Src can induce the apoptotic signal via c-Jun N-terminal kinase (JNK) activation. Here we report that the newly synthesized β-phenylacrylic acid derivatives, MHY791 and MHY1036 (MHYs), bind to epidermal growth factor receptor (EGFR) tyrosine kinase domains and function as EGFR inhibitors, having anti-cancer activities selectively in wild-type KRAS colon cancer. Mechanistically, MHYs-induced Src/JNK activation which enhanced their pro-apoptotic effects and therefore inhibition of Src by the chemical inhibitor PP2 or Src siRNA abolished the response. In addition, MHYs generated reactive oxygen species and increased ER stress, and pretreatment with antioxidant-inhibited MHY-induced ER

SUBMITTER: Kim SJ 

PROVIDER: S-EPMC6115383 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature