Curcumin and Resveratrol Induce Apoptosis and Nuclear Translocation and Activation of p53 in Human Neuroblastoma

Abstract

Background: Neuroblastoma (NB) is an aggressive childhood cancer of the peripheral nervous system arising from neural crest sympathoadrenal progenitor cells. Despite current rigorous treatment protocols, prognosis for high stage NB patients is poor and so there remains a need for more effective, less cytotoxic treatments. Curcumin and resveratrol possess anti-tumor properties in adult cancer models and negligible toxicity in normal cells, but little is known about the effect of these agents on pediatric cancers. Materials and Methods: Stage 4 MYCN-amplified NB cell lines, with wild-type or mutant p53, were treated with curcumin and resveratrol and analyzed for effects on proliferation, cell cycle, induction of apoptosis and p53 function. Results: Treatment induced a dose- and time-dependent decrease in cell viability, cell cycle arrest and induction of apoptosis. Treatment transiently up-regulated p53 expression and induced nuclear translocation of p53, followed by induction of p21^WAF-1/CIP-1 and Bax expression. Conclusion: Observations suggest that the cytotoxicity, cell cycle arrest and apoptosis induced by curcumin and resveratrol in NB cells may be mediated via functionally activated p53 and merit further study.