Atorvastatin: a potential chemopreventive agent in bladder cancer.
OBJECTIVE
To evaluate a commonly used 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor-atorvastatin-for potential activity against human bladder cancer. Patients with bladder cancer often have concomitant hyperlipidemia and cardiac disease due to common risk factors such as smoking and advanced age. As such, they are often prescribed HMG-CoA reductase inhibitors (statins), which have been suggested to affect tumor growth patterns.


METHODS
Two human transitional cell carcinoma cell lines--RT4 and KU-7--were exposed to atorvastatin at concentrations from 0 (control) to 100 microM for 48 or 72 hours. The effects on cell proliferation, DNA synthesis, and apoptosis were respectively evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and the thymidine incorporation assay and by quantifying DNA fragmentation by propidium iodide fluorescence and flow cytometry.


RESULTS
Atorvastatin inhibited cell proliferation and DNA synthesis in both bladder cancer cell lines. This led to significant cytotoxicity as demonstrated by DNA fragmentation and induction of apoptosis.


CONCLUSIONS
Atorvastatin exhibits significant antiproliferative and pro-apoptotic activity in human bladder cancer cells. This, coupled with its established clinical safety profile, provides a rationale for its use as a potential chemopreventive agent against bladder cancer.
Kamat
Ashish M
AM
Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. akamat@mdanderson.org
Nelkin
Gina M
GM
D000069059:Atorvastatin; D002295:Carcinoma, Transitional Cell / Q000517:prevention & control*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin