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Growth Arrest by Bufonis Venenum is Associated with Inhibition of Cdc2 and Cdc25C, and Induction of p21WAF1/CIP1 in T24 Human Bladder Carcinoma Cells  

Park Tae Yeol (Department of Otorhinolaryngology & Dermatology Dongeui University College of Oriental Medicine)
Park Cheol (Department of Biochemistry, Dongeui University College of Oriental Medicine and Research Institute of Oriental Medicine)
Yoon Hwa Jung (Department of Otorhinolaryngology & Dermatology Dongeui University College of Oriental Medicine)
Choi Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine and Research Institute of Oriental Medicine)
Ko Woo Shin (Department of Otorhinolaryngology & Dermatology Dongeui University College of Oriental Medicine)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.18, no.5, 2004 , pp. 1449-1455 More about this Journal
Abstract
Bufonis venenum (dried toad venom; Chinese name, Chan su) is a traditional Chinese medicine obtained from the skin venom gland of the toad. It has long been used in treating arrhythmia and other heart diseases in China and other Asian countries. Additionally, Bufonis venenum has been reported to selectively inhibit the growth of various lines of human cancer cells. In the present study, it was examined the effects of extract of Bufonis venenum (EBV) on the growth of human bladder carcinoma cell line T24 in order to investigate the anti-proliferative mechanism and induction of apoptosis by EBV. Treatment of T24 cells to EBV resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner. Flow cytometric analysis revealed that EBV treatment caused G2/M phase arrest of the cell cycle and down-regulation of cyclin A, cyclin B1 and Cdc2, which was associated with a marked up-regulation of cyclin-dependent kinases (Cdks) inhibitor p21 (WAF1/CIP1) in a p53-independent manner. The Cdc25C expression was also significantly inhibited by EBV treatment, however Wee1 kinase expression was not affected. The induction of apoptotic cell death by EBV was connected with down-regulation of anti-apoptotic Bcl-XS/L expression without alteration pro-apoptotic Bax expression. Taken together, these findings suggest that EBV may be a potential chemotherapeutic agent for the control of human bladder carcinorma cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of EBV.
Keywords
Bufonis Venenum; T24 bladder carcinoma; cell cycle; Cdc2; Cdc25C; inhibitor p21;
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