Inhibitory effects of curcumin on glioma and molecular mechanisms study

Objective:To elucidate the inhibitory effect and potential mechanisms of curcumin on glioma cells. Methods: Glioma cells U251 were treated with various concentrations of curcumin. Cell proliferation was measured by Maa-ja elintarvike-talouden tutkimuskeskus ( MTT) assay. The distribution of cells in the cell-cycle phases was determined using fluorescence-activated cell sorter (FACS) analysis of DNA content. After the treatment of 10μmol/L of curcumin for 24h, DNA fragment was electrophoresed on a 1% agarose gel, and examined after being stained with ethidium bromide. Cells were treated with or without curcumin(10 μmol/L) for 24 h and measured by Western blotting analysis, statistical difference was determined by student's t-test, or one-way ANOVA. Results: The treatment of curcumin significantly inhibited glioma cells U251 growth in vitro in a dose-dependent manner. FACS analysis showed that the low dose of curcumin induced significant G2/M phase of cell cycle arrest, and the high dose of curcumin increased G2/M phase of cell cycle arrest meanwhile induced significant S phase of cell cycle arrest. But no obvious pre-G1peak was observed at the different doses of curcumin. Genome DNA electrophoresis further confirmed that no DNA ladder was formed after the treatment of curcumin in U251 cells. Moreover, treatment of curcumin up-regulated p53 expression, followed by induction of p21WAF-1/CIP-1. Conclusion: The results demonstrate that curcumin has potent inhibitory action on glioma cell growth and proliferation via induction of cell cycle arrest instead of induction of apoptosis in a p53-dependent manner, and ING4 up-regulation possibly is in part involved in the signal pathways.