Dipyridamole intervention of breast cell carcinogenesis
Article first published online: 16 OCT 2012
Copyright © 2012 Wiley Periodicals, Inc.
How to Cite
Choudhary, S., Sood, S. and Wang, H.-C. R. (2012), Dipyridamole intervention of breast cell carcinogenesis. Mol. Carcinog.. doi: 10.1002/mc.21970
- Article first published online: 16 OCT 2012
- Manuscript Accepted: 22 SEP 2012
- Manuscript Revised: 16 JUL 2012
- Manuscript Received: 11 APR 2012
- breast cancer;
- environmental carcinogens;
- reactive oxygen species
Dietary prevention is a cost-efficient strategy to reduce the risk of human cancers. More than 85% breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens through a multistep and multiyear disease process. We used our chronically induced cellular carcinogenesis model as a target to search for preventive agents capable of blocking breast cell carcinogenesis. Dipyridamole (DPM), at a non-cytotoxic physiologically achievable dose of 10 nmol/L, effectively blocked breast cell carcinogenesis induced by cumulative exposures to three unrelated carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), benzo[a]pyrene (B[a]P), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The ability of DPM to block H-Ras upregulation, thus blocking ERK pathway activation, reactive oxygen species (ROS) elevation, and DNA damage in each exposure, may account for its mechanisms in intervention of carcinogenesis induced by cumulative exposures to PhIP. Likewise, DPM's ability to block ROS elevation and DNA damage may account for its mechanisms in intervention of carcinogenesis chronically induced by NNK and B[a]P, as well. DPM is approved by the Food and Drug Administration to control platelet aggregation and vasoconstriction in patients. Our study revealed, for the first time, the novel ability of DPM to block breast cell carcinogenesis induced by three unrelated carcinogens. DPM should be seriously considered as a chemopreventive agent in development of strategies for reducing the risk of sporadic breast cancer associated with long-term exposure to environmental carcinogens. © 2012 Wiley Periodicals, Inc.