title: Acetaldehyde and retinaldehyde-metabolizing enzymes in colon and pancreatic cancers.
abstract: Colorectal cancer (CRC) and pancreatic cancer are two very significant contributors to cancer-related deaths. Chronic alcohol consumption is an important risk factor for these cancers. Ethanol is oxidized primarily by alcohol dehydrogenases to acetaldehyde, an agent capable of initiating tumors by forming adducts with proteins and DNA. Acetaldehyde is metabolized by ALDH2, ALDH1B1, and ALDH1A1 to acetate. Retinoic acid (RA) is required for cellular differentiation and is known to arrest tumor development. RA is synthesized from retinaldehyde by the retinaldehyde dehydrogenases, specifically ALDH1A1, ALDH1A2, ALDH1A3, and ALDH8A1. By eliminating acetaldehyde and generating RA, ALDHs can play a crucial regulatory role in the initiation and progression of cancers. ALDH1 catalytic activity has been used as a biomarker to identify and isolate normal and cancer stem cells; its presence in a tumor is associated with poor prognosis in colon and pancreatic cancer. In summary, these ALDHs are not only biomarkers for CRC and pancreatic cancer but also play important mechanistic role in cancer initiation, progression, and eventual prognosis.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Mail Stop C238-P20, 12850 E Montview Blvd, Aurora, CO, 80045, USA.
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: J
authors.initials: J
authors.lastname: Arcaroli
authors.forename: D C
authors.initials: DC
authors.lastname: Thompson
authors.forename: W
authors.initials: W
authors.lastname: Messersmith
authors.forename: V
authors.initials: V
authors.lastname: Vasiliou
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000032:analysis*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D012172:Retinaldehyde / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D014212:Tretinoin; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D012172:Retinaldehyde