Antibiotic slows growth of bladder cancer cells in mice

An antibiotic used to treat urinary tract infections appears to slow or stop the growth of bladder cancer cells by blocking the formation of new blood vessels, according to results of a recent a study.

Researchers from the Johns Hopkins School of Medicine, Baltimore tested more than 177,000 chemical compounds and drugs for their ability to block the activity of a protein known as MetAP2, which has been implicated in the formation of new blood vessels. Of the 294 chemicals found to reduce MetAP2 activity by at least half, the antibiotic nitroxoline inhibited MetAP2 by more than 99% at a low and safe concentration.

The team also tested 2,687 FDA-approved drugs in the Johns Hopkins Drug Library for their ability to stop blood vessel-forming cells from growing. They grew human umbilical vein endothelial cells in tiny wells and treated each well with a different drug. Of the 210 drugs that inhibited cell growth by at least half, nitroxoline inhibited cell growth by 95.5%.

Although nitroxoline has not been approved by the FDA for clinical use, the authors said it is used as an antibiotic in several other countries, and therefore, was included in the drug library.

"Because nitroxoline showed such a substantial inhibitory effect, we moved on to see if it would have an effect on tumors in mice," said first author Jun O. Liu, PhD.

Mice carrying transplanted human bladder cancer cells were treated with nitroxoline injections every day for 2 weeks. Nitroxoline treatment reduced bladder cancer cell tumor volume by more than 50%.

"There are limitations of this study, but we find the results encouraging enough to pursue further study of nitroxoline for preclinical and clinical use in treating bladder carcinomas," Dr. Liu said.

Study results were published in the Journal of the National Cancer Institute (2010; 102:1855-73).