Abstract
The aim of the present study was to examine the impact of a four platinum complexes of formula [Pt2L4(berenil)2]Cl4 where L is 3-ethylpyridine (Pt10), 3-(n-butyl)pyridine (Pt11), 4- ethylpyridine (Pt12) and 4-(t-butyl)pyridine (Pt13) on viability of Ishikawa endometrial cancer cells using the MTT assay and inhibition of [3H]thymidine incorporation into DNA. Our results confirm that compounds Pt10-Pt13 are more potent antiproliferative agents than cisplatin in endometrial cancer cells. Moreover, it was shown that all examined compounds Pt10-Pt13 inhibit collagen biosynthesis in neoplastic cells stronger than cisplatin. Flow cytometric analysis after annexin V-FITC and propidium iodide staining confirmed also that apoptosis was the main response of Ishikawa endometrial cancer cells to Pt10-Pt13 treatment. Our results suggest that apoptosis of Ishikawa endometrial cancer cell lines 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.
Keywords: Apoptosis, cisplatin, cytotoxicity, dinuclear platinum complexes, Ishikawa endometrial cancer, flow cytometry.
Medicinal Chemistry
Title:Effects of Novel Alkyl Pyridine Platinum Complexes on Apoptosis in Ishikawa Endometrial Cancer Cells
Volume: 11 Issue: 6
Author(s): Robert Czarnomysy, Anna Bielawska, Anna Muszyńska and Krzysztof Bielawski
Affiliation:
Keywords: Apoptosis, cisplatin, cytotoxicity, dinuclear platinum complexes, Ishikawa endometrial cancer, flow cytometry.
Abstract: The aim of the present study was to examine the impact of a four platinum complexes of formula [Pt2L4(berenil)2]Cl4 where L is 3-ethylpyridine (Pt10), 3-(n-butyl)pyridine (Pt11), 4- ethylpyridine (Pt12) and 4-(t-butyl)pyridine (Pt13) on viability of Ishikawa endometrial cancer cells using the MTT assay and inhibition of [3H]thymidine incorporation into DNA. Our results confirm that compounds Pt10-Pt13 are more potent antiproliferative agents than cisplatin in endometrial cancer cells. Moreover, it was shown that all examined compounds Pt10-Pt13 inhibit collagen biosynthesis in neoplastic cells stronger than cisplatin. Flow cytometric analysis after annexin V-FITC and propidium iodide staining confirmed also that apoptosis was the main response of Ishikawa endometrial cancer cells to Pt10-Pt13 treatment. Our results suggest that apoptosis of Ishikawa endometrial cancer cell lines 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.
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Czarnomysy Robert, Bielawska Anna, Muszyńska Anna and Bielawski Krzysztof, Effects of Novel Alkyl Pyridine Platinum Complexes on Apoptosis in Ishikawa Endometrial Cancer Cells, Medicinal Chemistry 2015; 11 (6) . https://dx.doi.org/10.2174/1573406411666150206163547
DOI https://dx.doi.org/10.2174/1573406411666150206163547 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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