TY  - JOUR
T1  - NZ-419, a Radical Scavenger, Inhibits Intestinal Polyp Formation in Apc-Mutant Mice
A1  - Makoto Hosoya
A1  - Natsuki Kawashima
A1  - Shinichi Negishi
JF  - Bulletin of Pioneering Researches of Medical and Clinical Science
JO  - Bull Pioneer Res Med Clin Sci
SN  - 3006-2659
Y1  - 2022
VL  - 1
IS  - 1
DO  - 10.51847/EBGSUMgBcP
SP  - 32
EP  - 40
N2  - 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.
UR  - https://bprmcs.com/article/nz-419-a-radical-scavenger-inhibits-intestinal-polyp-formation-in-apc-mutant-mice-5kk2qmbyc23n0v7
ER  -