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Acetaldehyde and Retinaldehyde-Metabolizing Enzymes in Colon and Pancreatic Cancers

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Biological Basis of Alcohol-Induced Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Mail Stop C238-P20, 12850 E Montview Blvd, Aurora, CO, 80045, USA

    S. Singh

  2. Division of Medical Oncology, University of Colorado School of Medicine, Mail Stop C238-P20, 12850 E Montview Blvd, Aurora, CO, 80045, USA

    J. Arcaroli & W. Messersmith

  3. Department of Clinical Pharmacy, University of Colorado School of Medicine, Mail Stop C238-P20, 12850 E Montview Blvd, Aurora, CO, 80045, USA

    D. C. Thompson

  4. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA

    V. Vasiliou

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Correspondence to V. Vasiliou .

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Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the United States, Washington, District of Columbia, USA

    Samir Zakhari

  3. Centre of Alcohol Research, University of Heidelberg, Germany and Salem Medical Centre, Heidelberg, Germany

    Helmut K. Seitz

  4. Department of Pathology, Anatomy, & Cell, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jan B. Hoek

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Singh, S., Arcaroli, J., Thompson, D.C., Messersmith, W., Vasiliou, V. (2015). Acetaldehyde and Retinaldehyde-Metabolizing Enzymes in Colon and Pancreatic Cancers. In: Vasiliou, V., Zakhari, S., Seitz, H., Hoek, J. (eds) Biological Basis of Alcohol-Induced Cancer. Advances in Experimental Medicine and Biology, vol 815. Springer, Cham. https://doi.org/10.1007/978-3-319-09614-8_16

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