Corosolic acid inhibits colorectal cancer cells growth as a novel HER2/HER3 heterodimerization inhibitor

Background and Purpose Colorectal cancer is the third most common worldwide. HER2 HER3 are two members of human epidermal receptor family tyrosine kinase receptors (RTKs) associated with poor survival in colorectal cancer. They have been observed as important therapeutic targets various types Corosolic acid, a natural pentacyclic triterpene, has demonstrated to significant anti-cancer activity. However, target corosolic acid not yet explored. This study aimed reveal direct underlying its activities. Experimental Approach The were revealed by phospho-RTK array, bio-layer interferometry, co-immunoprecipitation, proximity ligation assay. inhibitory action on HER2/HER3 heterodimerization related downstream signalling investigated HCT116 SW480 cells. In addition, chemo-preventive effects validated both xenograft model AOM/DSS model. Key Results Our results that could prevent NRG1-induced suppress phosphorylation HER3. Furthermore, regulate pathways RalA/RalBP1/CDK1 PI3K/Akt/PKA, respectively, resulting changes Drp1 mitochondrial dynamics. exhibited activity Conclusions Implications Collectively, our directly targeted inhibited fission via regulating PI3K/Akt/PKA pathways, revealing novel mechanism beneficial