Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met.

Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met. J Zhejiang Univ Sci B. 2020 Oct.;21(10):779-795 Authors: Liu QQ, Zeng XL, Guan YL, Lu JX, Tu K, Liu FY Abstract Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Alk (containing parasitic fungi Hypomyces hyalines (Schw.) Tul.). Here, we initially found, by wound healing assay and Transwell assay in vitro, that verticillin A possesses an inhibitory effect against the migration and invasion of the human colon cancer cell. Subsequently, c-mesenchymal-epithelial transition factor (c-Met) was identified as a molecular target of verticillin A by screening key genes related to cell migration. Verticillin A-mediated c-Met suppression is at the transcriptional level. Further study demonstrated that verticillin A suppressed c-MET phosphorylation and decreased c-MET protein level. In addition, verticillin A inhibited the phosphorylation of c-MET downstream molecules including rat sarcoma (Ras)-associated factor (Raf), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). Overexpression of Erk partially reversed the verticillin A-mediated anti-metastasis action in the human colon cancer cell. More importantly, verticillin A also inhibited cancer cell metastasis in vivo. Thus, verticillin A can significantly inhibit the migration and invasion of colon cancer cells by targeting c-Met and inhibi...
Source: J Zhejiang Univ Sci ... - Category: Science Authors: Tags: J Zhejiang Univ Sci B Source Type: research