This article is more than 5 years old. Information may no longer be current.
Allopurinol inhibits expression of biomarkers in adenomatous colon polyps, adjacent tissue
Click Here to Manage Email Alerts
Allopurinol inhibits the expression of biomarkers beta-catenin and NF-kappa B, and may be a colorectal cancer-preventive compound in patients with colorectal adenomas, according to recent results.
In double blind, multicenter trial, researchers randomly assigned 73 adult patients with one or more colorectal adenomas to receive either placebo (n=24) or 100 mg allopurinol (n=24) or 300 mg allopurinol (n=25) daily for four weeks before polyp removal. Ki-67 labeling index in the adenomatous tissue was assessed before and after removal, along with immunohistochemical (HC) expression of NF-kappa B, beta-catenin, topoisomerase-II-alpha and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in polyps and the adjacent tissue.
Treated patients did not have different changes to Ki-67 (P=.5), topoisomerase-II-alpha (P=.6) or TUNEL (P=.7)expression compared with placebo recipients. Levels of beta-catenin (mean change –10.6%; P=.03) and NF-kappa B (–8.1%) decreased more from baseline in the adenomatous tissue among treated patients than placebo recipients.
A significantly larger decrease in NF-kappa B expression in polyp-adjacent normal tissue occurred among treated patients (mean change –16.4% from baseline; P=.01 compared with placebo recipients). This decrease was found to be dose-dependent (–12.4% for 100-mg dose and –14.6% for 300-mg dose; P=.013 for trend). No other significant differences in change to biomarker expression levels were observed in normal tissue between treated patients and placebo recipients.
Investigators said treatment was well tolerated throughout the cohort, with an overall mean of 98% for adherence. No adverse events of grade 2 or higher were reported.
“In this trial, the first to our knowledge ever conducted to assess the activity of allopurinol in reducing CRC [colorectal cancer] risk biomarkers in humans, we were unable to find any modulation of proliferation/apoptosis either in adenomatous or in normal colonic tissue,” the researchers wrote. “However, we found an activity of allopurinol in oxidative activation biomarkers of CRC.
“These findings, combined with the excellent drug safety profile and the very low cost, should encourage further investigations on allopurinol as a potential chemopreventive agent for adenoma recurrence and CRC.”
Click Here to Manage Email Alerts