Corosolic acid inhibits cancer progress through inactivating YAP in hepatocellular carcinoma.

Corosolic acid inhibits cancer progress through inactivating YAP in hepatocellular carcinoma. Oncol Res. 2020 Mar 27;: Authors: Jia M, Xiong Y, Li M, Mao Q Abstract Chemotherapy is critical for the treatment of hepatocellular carcinoma (HCC). Despite the pro-apoptotic effects of corosolic acid (CA) treatment, its underlying mechanism is not completely clear. The aim of this study was to determine the molecular mechanism of CA in HCC treatment. MTT assay was used to determine the IC50 of CA. Immunoprecipitation and immunofluorescence were used to detect the interaction between and subcellular localization of Yes-associated protein (YAP) and mouse double minute 2 (MDM2). In addition, in vivo xenotransplantation was performed to assess the effect of CA, YAP and MDM2 on tumorigenesis. The IC50 of CA was about 40 M in different HCC cell lines, and CA decreased YAP expression by reducing its stability and increasing its ubiquitination. CA treatment and MDM2 overexpression significantly decreased the crosstalk between YAP and cAMP-responsive element-binding protein (CREB), TEA domain transcription factor (TEAD), Runt-related transcription factor 2 (Runx2). CA stimulation promoted the translocation of YAP and MDM2 from the nucleus to the cytoplasm and increased their binding. In addition, CA treatment obviously reduced tumorigenesis, whereas this effect was abolished when cells were transfected with sh-MDM2 or Vector-YAP. The present stud...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research