Ursodeoxycholic acid and chemoprevention of colorectal cancer.
Colorectal cancer is respectively the third and second most common cancer among men and women in France. Interest in chemoprevention for colorectal cancer has increased over the last two decades. Beside non-steroidal anti-inflammatory drugs, ursodeoxycholic acid (UDCA) may have chemopreventive action in colorectal cancer with a likely better tolerance. In high-risk populations such as patients with inflammatory bowel disease or prior colorectal adenoma or carcinoma, retrospective and prospective studies have suggested a beneficial effect of UDCA. In azoxymethane model, UDCA inhibits tumor development by countering the tumor-promoting effects of secondary bile acids, such as deoxycholic acid (DCA). The opposing effects of UDCA and DCA on lipid raft composition may be central to their effects on colonic tumorigenesis. Differential effects of DCA and UDCA on growth factor and inflammatory signals involved in colorectal carcinogenesis, such as epidermal growth factor receptors (EGFR) signaling and Cox-2 expression, likely mediate their opposing effects on colonic tumor promotion and tumor inhibition, respectively.
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Service d'hépatologie, hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, université Pierre-et-Marie-Curie, 184 rue du Faubourg-Saint-Antoine, Paris cedex 12, France. lawrence.serfaty@sat.aphp.fr
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D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D019317:Evidence-Based Medicine; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014580:Ursodeoxycholic Acid; D051546:Cyclooxygenase 2; D066246:ErbB Receptors