LAB INVESTIGATION- HUMAN/ANIMAL TISSUE Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma

Abstract Gliomas are the most common and lethal pri-mary tumors of the central nervous system (CNS). Despite current rigorous treatment protocols, effect of chemother-apy has failed to improve patient outcome significantly. Curcumin is a potent antioxidant that possesses both anti-inflammatory and anti-tumor activities, can suppress the initiation, promotion, and metastasis of different tumors. Its anti-tumor properties in various cancer models and negli-gible toxicity in normal cells make it a promising chemo-therapeutic candidate. But the effect and the molecular mechanism of curcumin on gliomas are still recognized limitedly. The goal of the study is to elucidate the inhibi-tory effect and possible mechanisms of curcumin on gli-oma. After the treatment of curcumin, glioma cells U251 growth in vitro were significantly inhibited in a dose-dependent manner, and the low dose of curcumin induced G2/M cell cycle arrest. The high dose of curcumin not only enhanced G2/M cell cycle arrest, but also induced S phase of cell cycle arrest. But no obvious pre-G1 peak 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. Results of Western blot analysis demonstrated that ING4 expression was almost undetectable in U251 cells, but significantly up-regulated during cell cycle arrest induced by curcumin, and p53 expression was up-regulated followed by induction of p21WAF–1/CIP–1 and ING4. The results demonstrate that curcumin exerts 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 possibly is in part involved in the signal pathways