Robert Czarnomysy, Anna Bielawska, Anna Muszyńska and Krzysztof Bielawski Pages 540 - 550 ( 11 )
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.
Apoptosis, cisplatin, cytotoxicity, dinuclear platinum complexes, Ishikawa endometrial cancer, flow cytometry.
Department of Synthesis and Technology of Drugs, Medical University of Białystok, Kilińskiego 1, Bialystok 15-089, Poland