[Frontiers in Bioscience 11, 2007-2016, September 1, 2006]
Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells
Changping Zou 1, Jianwei Zhou 2, Linxin Qian 2, Jean M. Feugang 1, Jia Liu 2, Xinru Wang 2, Sheng Wu 2, Hong Ding2, Changchun Zou 1, Monica Liebert 3, and H. Barton Grossman 4
1Department of Obstetrics and Gynecology, University of Arizona, 2 The Key Laboratory of Reproductive Medicine and Department of Urology, the First Affiliated Hospital, Nanjing Medical University, 3 American Urology Association, 4 Departments of Urology, University of Texas M.D. Anderson Cancer Center
TABLE OF CONTENTS
Clinical trials have explored the use of natural and synthetic retinoids for the prevention of bladder cancer recurrence. Natural retinoids have been shown to inhibit bladder cancer growth. Here, we compared the effects of natural and synthetic retinoids in bladder cancer cells. Bladder cancer cell lines were treated with all-trans-retinoid acid (ATRA), N-4-hydroxyphenyl-retinamide (4-HPR) and 6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid (CD437). Their effects on cell growth, apoptosis, cell cycle, gene expression, and retinoid acid receptors (RARs) and the JWA-retinoid response gene were assessed. Most of the bladder cancer cells were resistant to ATRA (1 and 10 mM). 4-HPR inhibited cell growth by 90% at 10 mM; however, CD437 showed the same effect at 1 mM. 4-HPR and CD437 increased G1 and decreased S phase. The three retinoids differentially affected p53, RARs, and JWA. Only CD437 increased Caspase 3 expression. The results demonstrated that 4-HPR and CD437 were more potent growth inhibitors and apoptosis inducers than ATRA. However, 4-HPR was effective at a concentration at least 10 mM. The in vitro results suggested the higher dose of 4-HPR in chemoprevention trial be considered.