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Inhibition of cell proliferation by novel pyridine platinium(II) complexes on the Ishikawa endometrial cancer cell lines

Robert Czarnomysy 1,  Anna Muszyńska 1,  Anna Bielawska 2,  Agnieszka Gornowicz 2,  Krzysztof Bielawski 1

1. Department of Medical Chemistry and Drug Technology, Medical University of Białystok, Białystok 15-089, Poland
2. Medical University of Bialystok, Department of Biotechnology, Kilinskiego 1, Białystok 15-089, Poland

Abstract
The aim of this study was to compare the effect of cisplatin and novel dinuclear platinum(II) complexes with berenil and pyridine ligands on the Ishikawa endometrial cancer cell line. The chemical formula is [Pt2L4(berenil)2]Cl4, where L is 3-ethylpyridine (Pt10), 3-(n-butyl)pyridine (Pt11), 4-ethylpyridine (Pt12) and 4-(t-butyl)pyridine (Pt13). The results showed higher cytotoxicity of Pt10-Pt13 compounds in comparison with cisplatin on the Ishikawa endometrial cancer cell line. In relation to human skin fibroblasts, Pt10-Pt13 compounds were characterized with lower cytotoxicity than in case of examined neoplastic cells. Moreover, it was shown that all examined compounds Pt10-Pt13 inhibit DNA biosynthesis and collagen biosynthesis in the Ishikawa endometrial cancer cell line stronger than in human skin fibroblasts. The influence of berenil complexes of Pt10-Pt13 on apoptosis induction in the cancer cell lines was evaluated with the use of the flow cytometry and the fluorescent microscope. The Pt10-Pt13 compounds showed higher ability to induce apoptosis in the Ischikawa endometrial carcinoma cells in comparison with cisplatin. The results suggest that apoptosis of cells in the presence of Pt10-Pt13 follows the mitochondrial pathway, with the decrease in mitochondrial membrane potential and activation of caspase 9, as well as by the external pathway with the significant increase in FADD protein expression and caspase 8. The determination of caspase 3 activity with the flow cytometry using the antibody recognizing the active form of this protein in the process of apoptosis showed that caspases cascade was started, particularly effector caspase 3, engaged in the executive phase of apoptosis. The obtained results in the present study demonstrated the cytotoxic activity of new berenil complexes of platinum(II) can be connected with their ability to impair of DNA biosynthesis and induction of apoptosis.

 

 

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Presentation: Poster at IX Multidyscyplinarna Konferencja Nauki o Leku, by Krzysztof Bielawski
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-03-14 11:26
Revised:   2014-04-28 18:39