Administration of High-Dose Vitamin C and Irinotecan Ameliorates Colorectal Cancer Induced by Azoxymethane and Dextran Sodium Sulfate in Mice

• Published in: Biological & pharmaceutical bulletin 2018/12/01, Vol.41(12), pp.1797-1803
• Main Authors: Kondo, Kanako, Sano, Reimi, Goto, Kenji, Hiramoto, Keiichi, Ooi, Kazuya
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antitumor activity; Apoptosis - drug effects; Ascorbic acid; Ascorbic Acid - administration & dosage; Ascorbic Acid - therapeutic use; Azoxymethane; Cancer; Caspase; Caspase-1; Collagen (type I); Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - chemically induced; Colorectal Neoplasms - pathology; Colorectal Neoplasms - prevention & control; Dextran; dextran sodium sulfate; Dextran Sulfate; DNA nucleotidylexotransferase; Dose-Response Relationship, Drug; Drug Synergism; Interleukin 6; Interleukin-6 - blood; Irinotecan; Irinotecan - administration & dosage; Irinotecan - therapeutic use; Male; Mice; Mice, Hairless; Neutrophils; Reactive oxygen species; Reactive Oxygen Species - blood; Sodium; Sodium sulfate; Sulfates; Vitamin C
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00453

High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.