The anti-ischemia agent ranolazine promotes the development of intestinal tumors in APC(Min/+) mice.
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.
Suckow
Mark A
MA
Walther Cancer Center, 400 Freimann Life Science Center, University of Notre Dame, Notre Dame, IN 46556, USA. suckow.1@nd.edu
Gutierrez
Linda S
LS
Risatti
Christina A
CA
Wolter
William R
WR
Taylor
Richard E
RE
Pollard
Morris
M
Navari
Rudolph M
RM
Castellino
Francis J
FJ
Paoni
Nicholas F
NF
D000083:Acetanilides; D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000473:pathology*; D000483:Alleles; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D017491:Genes, APC; D007274:Injections, Intraperitoneal; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000473:pathology; D010879:Piperazines / Q000633:toxicity*; D000069458:Ranolazine
D000083:Acetanilides; D002273:Carcinogens; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine