Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma.
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.


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.


CONCLUSIONS
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.
Liontas
Aristotle
A
Department of Paediatric Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Yeger
Herman
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D003474:Curcumin; D000077185:Resveratrol