Ranolazine was shown to improve exercise parameters in patients with chronic angina. It works by switching myocardial energy metabolism from fatty acids to glucose, thus increasing the efficiency of ATP production under hypoxic conditions. Tumors are hypoxic and may also respond to ranolazine. We found that ranolazine caused a dose-dependent increase in tumor number in APC (Min/+) mice, a model of spontaneous intestinal tumorigenesis. Tumors from drug-treated mice were also more dysplastic and invasive than those from untreated mice. These findings have implications for the use of ranolazine in patients with a history of malignant neoplasms or adenomatous polyps.
Bibliographical noteFunding Information:
This work was done in collaboration with the Walter Cancer Institute, Indianapolis, IN, and funding was provided by the Walther Cancer Research Center, University of Notre Dame. The authors are grateful to the staff in the histology facility of the W.M. Keck Center for Transgene Research for preparing the H and E stained slides. We also want to thank Matthew Feldman for his help in preparing the figures.