Combined effect of chemopreventive agent N-(4-hydroxyphenyl) retinamide (4-HPR) and gamma-radiation on bladder cancer cell lines.
The incidence of bladder cancer has increased in the United States during the past 50 years, consistent with increased exposure to bladder carcinogens in the environment and tobacco use. Although N-(4-hydroxyphenyl) retinamide (4-HPR), a retinoid derivative, has been used as a chemopreventive agent of bladder cancer in clinical trials, little is known about its mechanisms of action against bladder cancer cells. Previous studies suggest this chemopreventive agent may inhibit tumor growth by inducing apoptosis. To further investigate this putative effect, we examined the effect of 4-HPR and gamma-radiation and their combined effects in three selected bladder cancer cell lines. Indeed, 4-HPR induced apoptosis in these cell lines in a dose-dependent manner. A 2.5 microM dose of 4-HPR and 50 rad of gamma-irradiation induced about 10% increase in apoptotic cells, respectively. However, this low dose 4-HPR combined with low dose gamma-irradiation had a synergistic effect on apoptosis, in which apoptotic cells increased by more than 30%. The findings have potential clinical implications and warrant further investigations both in vitro and in vivo in bladder cancer.
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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Zou
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Wang
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Liebert
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Grossman
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Lotan
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Wei
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D018890:Chemoprevention; D002842:Chromatids / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D017313:Fenretinide / Q000494:pharmacology* / Q000627:therapeutic use; D005720:Gamma Rays / Q000627:therapeutic use*; D006801:Humans; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control* / Q000532:radiotherapy
D000970:Antineoplastic Agents; D017313:Fenretinide