Casticin induces human glioma cell death through apoptosis and mitotic arrest.

BACKGROUND: Malignant gliomas are the leading cause of morbidity and mortality in brain and central nervous system tumors. Recently, casticin has drawn wide attention to its critical role in tumor progression. However, the effect of casticin on glioma remains undefined.
METHODS: Following treatment with casticin, cell viability, apoptosis, and cell cycle arrest were examined in U251 glioma cells. Additionally, the involved molecular mechanism was assessed by western blotting and flow cytometry.
RESULTS: Casticin triggered an obvious dose-dependent decrease in U251, U87 and U373 glioma cell viability, and the growth inhibitory effect of casticin was correlated with cell cycle arrest and cell apoptosis. Further mechanistic analysis indicated that casticin induced G2/M phase arrest by attenuating the polymerization of tubulin. Furthermore, striking apoptosis was also confirmed, accompanied by the up-regulation of caspase-3, p53 and proapoptotic protein Bax. These effects were absent when the caspase inhibitor z-VAD-fmk or p53 inhibitor PFTα were applied, suggesting that casticin could trigger cell apoptosis in a caspase-3 and p53-dependent manner.
CONCLUSION: These findings provide a prominent insight into how casticin abrogates the pathogenesis of glioma, and support its potential clinical prospect for further development of anti-brain cancer therapy.