Document Detail


Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells.
MedLine Citation:
PMID:  9764849     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.
Authors:
S H Jee; S C Shen; C R Tseng; H C Chiu; M L Kuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  111     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-10-29     Completed Date:  1998-10-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  656-61     Citation Subset:  IM    
Affiliation:
Department of Dermatology, College of Medicine, National Taiwan University, Taipei.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Biological Markers / analysis
Carcinoma, Basal Cell / pathology*
Cell Cycle / drug effects
Curcumin / pharmacology
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / drug effects
DNA-Binding Proteins / physiology
Humans
Intracellular Signaling Peptides and Proteins
Oligonucleotides, Antisense / pharmacology
Proteins / drug effects
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / analysis,  genetics,  pharmacology
Chemical
Reg. No./Substance:
0/Biological Markers; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/DNA-Binding Proteins; 0/GADD45 protein; 0/Intracellular Signaling Peptides and Proteins; 0/Oligonucleotides, Antisense; 0/Proteins; 0/Tumor Suppressor Protein p53; 458-37-7/Curcumin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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