The Spindle Damage and Mitotic Catastrophe in Hepato-carcinoma HepG2 Cells Induced by Bromovanin BVAN08

Abstract: To investigate the induction of bromovanin (6-bromine-5-hydroxy-4-methoxy-benzaldehyde， BVAN08) on the spindle damage and mitotic catastrophe of cancer cells and its related mechanism， and to provide more solid evidence and experimental data for exploring bromovanin as anticancer new drug. Cellular morphology changes after bromovanin treatment were observed by light microscope， flow cytometry was used to detect cell cycle， spindle checkpoint analysis and immunostaining experiment were performed to investigate the effect of bromovanin on process of mitotic division and spindle structure. Western blot analysis was used to determine protein expression changes. The results demonstrated that HepG2 cells were become rounding and detached quickly after treated with 20-60 μmol/L of bomovanin， and at last dead in a dose-dependent manner. Bromovanin treatment resulted in a G₂/M arrest， increased mitotic index and considerable ratio of non-diploid or polyploidy cells. Our result also demonstrated the destruction of spindle structure as expressed by multiple centrosome. FoxM1， a cell cycle control associated transcription regulation factor and its downstream target molecules cyclinB1 and Cdk1 were down-regulated， and accompanying with the mitotic catastrophe. This study demonstrated that bromovanin destroyed spindle structure， induced mitotic arrest and catastrophe. Inactivation of FoxM1 protein could involve in the effective mechanism of bromovanin.
    

CSTR: 32200.14.cjcb.2008.05.0016