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Korean J Urol Oncol > Volume 6(2); 2008 > Article
The Korean Journal of Urological Oncology 2008;6(2): 92-99.
인체 방광암과 신세포암에 미치는 Valproic Acid의 선택적 항암효과
김명, Fernando Kim, 정성진, 홍성규, 이은식, 이상은, 변석수
서울대학교 의과대학 비뇨기과학교실, 1Division of Urology, Department of Surgery, University of Colorado School of Medicine, Denver, CO, USA
A Selective Anticancer Effect of Valproic Acid in Human Bladder and Renal Cancer Cells
Myong Kim , Fernando Kim , Seong Jin Jeong , Sung Kyu Hong , Eunsik Lee , Sang Eun Lee , Seok-Soo Byun
Department of Urology, Seoul National University College of Medicine, Seoul, Korea and 1Division of Urology, Department of Surgery, University of Colorado School of Medicine, Denver, CO, USA
Published online: August 30, 2008.
Valproic acid(VPA) has been used as an antiepileptic agent for a long time. Recently, it has been reported to have multiple anticancer mechanisms. We investigated its effect on growth inhibition of two human bladder cancer cell lines(HTB5 and HTB9) and our two primarily cultured renal cell carcinoma (RCC) cell lines (Kiko21 and Kiko22).
Materials and Methods:
The DNA synthesis capacity, cell cycle analysis, clonogenic and invasion assays were performed. We also studied Western blot of cell cycle-related regulators and apoptosis-related proteins to evaluate its anticancer mechanism in the bladder tumor cell lines.
Acute VPA administration(1-10mM for 24-72 hours) suppressed tumor cell proliferation in a time- and dose-dependent manner(p<0.05) in all two bladder tumor cell lines. However, growth of the two RCC cell lines was not influenced by VPA application, even in the highest dose of 10mM. The cpm count ratio of the VPA-treated bladder cancer cells decreased in a dose-dependent manner. VPA induced G1 phase cell cycle arrest effectively in both bladder cell lines. A significant decrease in colony number and invasiveness was seen with the VPA treatment in the two bladder cell lines. Western blot analysis revealed up-regulated p21 and down-regulated cyclin A with the increasing concentrations of VPA in both bladder cell lines.
Our results suggest a selective characteristic of VPA in inhibiting cancer growths and its potential role as an agent for preventing recurrence of superficial bladder cancer and progression of muscle-invasive disease. (Korean J Urol Oncol 2008;6:92-99)
Key Words: Urinary bladder; Urinary bladder neoplasms; Kidney neoplasms; Valproic acid; Histone deacetylases
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