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

Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Aik(containing parasitic fungi Hypomyces hyalines(Schw.)Tul.).Here,we initially found,by wound healing assay and Tran swell assay in vitro,that verticilli n A possesses an inhibitory effect agai nst the migrati on and in vasion 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 suppress!on is at the transcriptio nal level.Further study dem on strated that verticilli n 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 inhibiting Ras/Raf/mitogen-activated extracellular signal-regulated kinase(MEK)/ERK signaling pathways.Therefore,we determined that verticillin A is a natural compound that can be further developed as an anti-metastatic drug in human cancers.

粉红粘帚霉1A毒杀线虫活性代谢物的研究

在研究粉红粘帚霉Gliocladium roseum 1A抗线虫活性代谢产物的过程中,活性跟踪分离获得4个化合物。通过UV、IR、MS、1HN-MR、13CN-MR、DEPT、1H-1HCOSY、HMQC、HMBC等波谱分析,鉴定其结构分别与轮枝菌素A、11'-脱氧轮枝菌素、sch52900和sch52901相同。首次报道这4个化合物对线虫的毒杀活性。