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Proapoptotic effects of new pentabromobenzylisothioureas and CK2 inhibitor in prostate adenocarcinoma cell line |
Mirosława Koronkiewicz 1, Zygmunt Kazimierczuk 2, Kinga Szarpak 1, Zdzisław Chilmonczyk 1 |
1. National Medicines Institute (NIL), Chełmska 30/34, Warsaw 00-725, Poland |
Abstract |
Prostate cancer is one of the most common cancers in elderly men in the Western world. Its growth is dependent on androgens and androgen receptor signaling. Androgen ablation by orchidectomy and/or treatment with LHRH-analogs or anti-androgens are the most common therapy strategies. Chemical castration often leads to a selection of hormone-refractory cells, which are mostly characterized by activation of anti-apoptotic signaling pathways. The agents capable of inducing apoptosis in prostate cancer cells seems a promising approach to treatment of this malignancy. In prostate cancer cells seems a promising approach to treatment of this malignancy. In this study we describe the synthesis of several new modified S-2,3,4,5,6-pentabromobenzylisothiouronium bromides and their activity against human prostate adenocarcinoma PC-3 cell line. All the tested compounds induced apoptosis and cytostatic effect in the tested cancer line. Apoptosis induced by the most effective compounds ZKK-3, ZKK-9 and ZKK-13 (20 μM) was 41,5%, 46,3% and 65,7% respectively, after 48h incubation time. We also determined synergetic effects of combination of two selected S-2,3,4,5,6-pentabromobenzylisothiouronium bromides (ZKK-3, ZKK-9) with new casein kinase II inhibitor 2-(4-methylpiperazin-1-yl)-4,5,6,7-tetrabromo-1H-benzimidazole (TBIPIP) in prostate cancer PC-3 cell line. Flow cytometry analysis were run on a FACSCaliur Flow Cytometer (Becton Dickinson Co., San Jose, CA, USA). Acknowledgment This study was supported by the Ministry of Science and Higher Education (Poland), grant No. N N209 371439. |
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Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Mirosława KoronkiewiczSee On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku Submitted: 2012-03-15 13:53 Revised: 2012-04-10 13:33 |