Review
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World J Gastrointest Oncol. Mar 15, 2014; 6(3): 55-66
Published online Mar 15, 2014. doi: 10.4251/wjgo.v6.i3.55
The role of antioxidants and pro-oxidants in colon cancer
William L Stone, Koyamangalath Krishnan, Sharon E Campbell, Victoria E Palau
William L Stone, Department of Pediatrics, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States
Koyamangalath Krishnan, Department of Internal Medicine, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States
Sharon E Campbell, Department of Biochemistry, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States
Victoria E Palau, Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, United States
Author contributions: Stone WL contributed to the study idea, study design, literature search, manuscript writing and the final revision of the article; Krishnan K contributed to the manuscript writing and the final revision of the article; Campbell SE contributed to the manuscript writing and the final revision of the article; Palau VE contributed to the manuscript writing and the final revision of the article.
Correspondence to: William L Stone, PhD, Professor, Department of Pediatrics, James H Quillen College of Medicine, East Tennessee State University, Box 70578, Dogwood Lane, Johnson City, TN 37614, United States. stone@etsu.edu
Telephone: +1-423-4398762 Fax: +1-423-4398066
Received: November 21, 2013
Revised: January 14, 2014
Accepted: February 16, 2014
Published online: March 15, 2014
Processing time: 119 Days and 15.2 Hours
Abstract

This review focuses on the roles antioxidants and pro-oxidants in colorectal cancer (CRC). Considerable evidence suggests that environmental factors play key roles in the incidence of sporadic CRC. If pro-oxidant factors play an etiological role in CRC it is reasonable to expect causal interconnections between the well-characterized risk factors for CRC, oxidative stress and genotoxicity. Cigarette smoking, a high dietary consumption of n-6 polyunsaturated fatty acids and alcohol intake are all associated with increased CRC risk. These risk factors are all pro-oxidant stressors and their connections to oxidative stress, the intestinal microbiome, intestinal microfold cells, cyclooxygenase-2 and CRC are detailed in this review. While a strong case can be made for pro-oxidant stressors in causing CRC, the role of food antioxidants in preventing CRC is less certain. It is clear that not every micronutrient with antioxidant activity can prevent CRC. It is plausible, however, that the optimal food antioxidants for preventing CRC have not yet been critically evaluated. Increasing evidence suggests that RRR-gamma-tocopherol (the primary dietary form of vitamin E) or other “non-alpha-tocopherol” forms of vitamin E (e.g., tocotrienols) might be effective. Aspirin is an antioxidant and its consumption is linked to a decreased risk of CRC.

Keywords: Colorectal cancer; Vitamin E; Tocopherols; Tocotrienols; Oxidative stress; Microbiome; Intestinal; Cyclooxygenase-2; Intestinal microfold cells; Alcohol; Cigarette smoke; Antioxidants; Genotoxicity

Core tip: This review summarizes the roles that antioxidant and pro-oxidant factors play in the development of colorectal cancer (CRC). This review is timely since our understanding of the roles these factors play in CRC has made major advances and is now ripe for translational research efforts. A systems biology research approach appears to be optimal since environmental pro-oxidative stress factors (such as cigarette smoking, a high dietary consumption of n-6 polyunsaturated fatty acids and alcohol intake) are likely to interact with the intestinal microbiome causing genotoxic damage to the epithelial cells of the large intestine and CRC.