2022 Volume 1 Issue 1
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NZ-419, a Radical Scavenger, Inhibits Intestinal Polyp Formation in Apc-Mutant Mice


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  1. Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
  2. Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
  3. Central Radioisotope Division, National Cancer Center Research, Tokyo 104-0045, Japan.
  4. Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Abstract

Colorectal cancer ranks as the fourth most common cause of cancer-related mortality worldwide, making the development of preventive strategies a critical priority. Antioxidants have been considered as potential preventive agents; however, the contribution of their direct radical-scavenging activity to cancer prevention remains uncertain. In this study, we investigated whether NZ-419, a hydroxyl radical scavenger, could suppress colorectal tumorigenesis through direct elimination of reactive oxygen species (ROS). NZ-419, a metabolite of creatinine with proven safety and prior efficacy in delaying chronic kidney disease progression in rats, is currently under clinical evaluation. Our findings revealed that NZ-419 significantly reduced ROS production in HCT116 cells exposed to H₂O₂ and downregulated H₂O₂-induced transcriptional activation of the Nrf2 promoter. Oral supplementation of 500 ppm NZ-419 to Apc-mutant Min mice for 8 weeks resulted in a marked reduction of small intestinal polyps, particularly in the middle region, lowering polyp numbers to 62.4% of those in untreated controls (p < 0.05). As anticipated, NZ-419 treatment altered serum levels of reactive carbonyl species, serving as oxidative stress indicators. Furthermore, polyp tissues from treated mice exhibited decreased expression of the proliferation-related oncogene c-Myc, accompanied by modest suppression of epithelial cell proliferation assessed via PCNA staining. Collectively, these results indicate that NZ-419 inhibits intestinal polyp formation in Min mice, highlighting the potential of radical scavenger-based antioxidants as chemopreventive agents against colorectal cancer.


How to cite this article
Vancouver
Hosoya M, Kawashima N, Negishi S. NZ-419, a Radical Scavenger, Inhibits Intestinal Polyp Formation in Apc-Mutant Mice. Bull Pioneer Res Med Clin Sci. 2022;1(1):32-40. https://doi.org/10.51847/EBGSUMgBcP
APA
Hosoya, M., Kawashima, N., & Negishi, S. (2022). NZ-419, a Radical Scavenger, Inhibits Intestinal Polyp Formation in Apc-Mutant Mice. Bulletin of Pioneering Researches of Medical and Clinical Science, 1(1), 32-40. https://doi.org/10.51847/EBGSUMgBcP
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