Dual-mode interaction between quercetin and DNA-damaging drugs in cancer cells.
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.


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.


CONCLUSIONS
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.
Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA. tsamuel@mytu.tuskegee.edu
Temesgen
T
Samuel
Khalda
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Fadlalla
Lachundra
L
Mosley
Venkat
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Katkoori
Timothy
T
Turner
Upender
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Manne
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002166:Camptothecin / Q000008:administration & dosage; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056744:Cyclin B1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D000077022:Survivin; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; C494826:BAX protein, human; C107489:BIRC5 protein, human; C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005047:Etoposide; D011794:Quercetin; D005472:Fluorouracil; D002166:Camptothecin