Document Detail


Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cells.
MedLine Citation:
PMID:  20472336     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Curcumin from the rhizome of theCurcuma longa plant has chemopreventative activity and inhibits the growth of neoplastic cells. Since p53 has been suggested to be important for anticancer activity by curcumin, we investigated curcumin-induced cytotoxicity in cultures of p53(+/+) and p53(-/-) HCT-116 colon cancer cells, as well as mutant p53 HT-29 colon cancer cells. Curcumin killed wild-type p53 HCT-116 cells and mutant p53 HT-29 cells in a dose- and time-dependent manner. In addition, curcumin-treated p53(+/+) HCT-116 cells and mutant p53 HT-29 cells showed upregulation of total and activated p53, as well as increased expression of p53-regulated p21, PUMA (p53 upregulated modulator of apoptosis), and Bax; however, an equivalent cytotoxic effect by curcumin was observed in p53(+/+) and p53(-/-) HCT-116 cells, demonstrating that curcumin-induced cytotoxicity was independent of p53 status. Similar results were obtained when the cytotoxic effect of curcumin was assessed in wild-type p53 HCT-116 cells after siRNA-mediated p53 knockdown. Chromatin condensation, poly (ADP-ribose) polymerase-1 cleavage and reduced pro-caspase-3 levels in curcumin-treated p53(+/+) and p53(-/-) HCT-116 cells suggested that curcumin caused apoptosis. In addition, exposure to curcumin resulted in superoxide anion production and phosphorylation of oxidative stress proteins in p53(+/+) and p53(-/-) HCT-116 cells. Collectively, our results indicate that, despite p53 upregulation and activation, curcumin-induced apoptosis in colon cancer cells was independent of p53 status and involved oxidative stress. Curcumin may therefore have therapeutic potential in the management of colon cancer, especially in tumorsthatare resistant to conventional chemotherapydue todefects inp53 expression or function.
Authors:
Jane L Watson; Richard Hill; Paul B Yaffe; Anna Greenshields; Mark Walsh; Patrick W Lee; Carman A Giacomantonio; David W Hoskin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-15
Journal Detail:
Title:  Cancer letters     Volume:  297     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / metabolism
Caspase 3 / metabolism
Cell Survival / drug effects
Chromatin Assembly and Disassembly / drug effects
Colonic Neoplasms / genetics,  metabolism,  pathology*
Curcumin / pharmacology*
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Dose-Response Relationship, Drug
HCT116 Cells
HT29 Cells
Humans
Mutation
Oxidative Stress / drug effects*
Phosphorylation
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins / metabolism
RNA Interference
Superoxides / metabolism*
Time Factors
Tumor Suppressor Protein p53 / genetics,  metabolism*
Up-Regulation
bcl-2-Associated X Protein / metabolism
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Apoptosis Regulatory Proteins; 0/BAX protein, human; 0/BBC3 protein, human; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Proto-Oncogene Proteins; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 11062-77-4/Superoxides; 458-37-7/Curcumin; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3

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


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