Document Detail


Dual-mode interaction between quercetin and DNA-damaging drugs in cancer cells.
MedLine Citation:
PMID:  22213289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: DNA-damaging drugs constitute standard chemotherapy regimen for advanced colorectal cancer. Here, the interactions between quercetin and 5-fluorouracil (5-FU), etoposide, and camptothecin were examined in cancer cells.
MATERIALS AND METHODS: HCT116 colorectal or PPC1 prostate cancer cells were treated with quercetin and the drugs. Clonogenicity assays, cell cycle profiles, and expressions of p53, p21, BAX, survivin and cyclin B1 proteins were used to examine the effects of the treatments.
RESULTS: Quercetin synergistically inhibited the clonogenicity of the wild-type cells, but inhibited the cell cycle effects of all the drugs tested. In p53-null cells, the combination of low dose 5-FU with up to 6 μM quercetin promoted clonogenic survival. Treatment of p53-wild-type cells with 50 μM quercetin reduced drug-induced up-regulation of p53, p21 and BAX. The combination of quercetin and the drugs also reduced the levels of cyclin B1 and survivin proteins.
CONCLUSION: While high doses of quercetin synergize with DNA-damaging agents, the effect of drug combination with quercetin is influenced by the effective doses and the p53 status of the cells.
Authors:
Temesgen Samuel; Khalda Fadlalla; Lachundra Mosley; Venkat Katkoori; Timothy Turner; Upender Manne
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-03     Completed Date:  2012-02-24     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  61-71     Citation Subset:  IM    
Affiliation:
Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA. tsamuel@mytu.tuskegee.edu
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antioxidants / pharmacology*
Apoptosis / drug effects
Blotting, Western
Camptothecin / administration & dosage
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Colorectal Neoplasms / drug therapy*,  metabolism,  pathology
Cyclin B1 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
DNA Damage / drug effects*
Drug Synergism
Etoposide / administration & dosage
Flow Cytometry
Fluorouracil / administration & dosage
Humans
Inhibitor of Apoptosis Proteins / metabolism
Male
Prostatic Neoplasms / drug therapy*,  metabolism,  pathology
Quercetin / pharmacology*
Tumor Stem Cell Assay
Tumor Suppressor Protein p53 / metabolism
bcl-2-Associated X Protein / metabolism
Grant Support
ID/Acronym/Agency:
2 U54 CA118948-06/CA/NCI NIH HHS; G12 MD007585/MD/NIMHD NIH HHS; G12 RR003059/RR/NCRR NIH HHS; G12RR003059/RR/NCRR NIH HHS; SC2 CA138178/CA/NCI NIH HHS; SC2CA138178/CA/NCI NIH HHS; U54 CA118638/CA/NCI NIH HHS; U54 CA118948/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/BAX protein, human; 0/BIRC5 protein, human; 0/CCNB1 protein, human; 0/CDKN1A protein, human; 0/Cyclin B1; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Inhibitor of Apoptosis Proteins; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 117-39-5/Quercetin; 33419-42-0/Etoposide; 51-21-8/Fluorouracil; 7689-03-4/Camptothecin
Comments/Corrections

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