Chlorogenic acid differentially alters hepatic and small intestinal thiol redox status without protecting against azoxymethane-induced colon carcinogenesis in mice.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. Epidemiological data have suggested that coffee consumption is inversely related to CRC risk, which may be attributed to chlorogenic acid (CGA), an ester of caffeic acid (CA) and quinic acid. This study was conducted to determine whether chronic dietary CGA supplementation would attenuate tumorigenesis and oxidative stress in a mouse model of azoxymethane (AOM)-induced colon cancer. Mice (4-wk old; n = 15/group) were fed CGA (0%, 0.01%, or 0.1%) for 20 wk and received 6 weekly intraperitoneal AOM injections (10 mg/kg). CGA and CA dose-dependently accumulated in the small intestinal mucosa. AOM induced (P < 0.05) colonic aberrant crypt foci (14.2 +/- 1.9/field) and tumors (14.6 +/- 1.1/colon), which were correlated (r = .677; P < 0.05), and CGA at either dose did not reduce tumorigenesis. Hepatic GSH/GSSG and Cys/CySS ratios were unaffected by AOM, but CGA at 0.1% increased these ratios by decreasing GSSG and CySS. CGA did not affect the ratios of small intestinal GSH/GSSG or Cys/CySS, which were decreased in response to AOM treatment. Collectively, these data indicated that CGA did not protect against AOM-induced tumorigenesis but affected hepatic thiol redox status in this colon cancer model.
Park
Hea Jin
HJ
University of Connecticut, Storrs, Connecticut 06269-4017, USA.
Davis
Steven R
SR
Liang
Hsin-Yin
HY
Rosenberg
Daniel W
DW
Bruno
Richard S
RS
D000818:Animals; D001397:Azoxymethane; D001835:Body Weight; D002726:Chlorogenic Acid / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004435:Eating; D005978:Glutathione / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D002726:Chlorogenic Acid; D005978:Glutathione; D001397:Azoxymethane