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Acetaldehyde and Retinaldehyde-Metabolizing Enzymes in Colon and Pancreatic Cancers

  • S. Singh
  • J. Arcaroli
  • D. C. Thompson
  • W. Messersmith
  • V. Vasiliou
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 815)

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.

Keywords

Acetaldehyde ALDH Biomarker Colorectal cancer Pancreatic cancer Retinaldehyde Stem cells 

Notes

Acknowledgments

We would like to thank our colleagues for critically reviewing this manuscript. This work was supported, in part, by the following NIH grants; AA022057 and EY11490.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • S. Singh
    • 1
  • J. Arcaroli
    • 2
  • D. C. Thompson
    • 3
  • W. Messersmith
    • 2
  • V. Vasiliou
    • 4
  1. 1.Department of Pharmaceutical SciencesUniversity of Colorado Anschutz Medical CampusAuroraUSA
  2. 2.Division of Medical OncologyUniversity of Colorado School of MedicineAuroraUSA
  3. 3.Department of Clinical PharmacyUniversity of Colorado School of MedicineAuroraUSA
  4. 4.Department of Environmental Health SciencesYale School of Public HealthNew HavenUSA

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