The ruthenium complexes cis-(dichloro)tetramineruthenium(III) chloride and cis-tetraammine(oxalato)ruthenium(III) dithionate overcome resistance inducing apoptosis on human lung carcinoma cells (A549)

作者: Cesar Augusto Sam Tiago Vilanova-Costa , Hellen Karine Paes Porto , Flávia de Castro Pereira , Aliny Pereira de Lima , Wagner Batista Dos Santos

DOI: 10.1007/S10534-014-9715-X

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摘要: Lung cancer is one of the leading causes death in world, and non-small cell lung carcinoma accounts for approximately 75–85 % all cancers. In present work, we studied antitumor activity compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl2(NH3)4]Cl} against human tumor line A549. The study aimed to investigate relationship between expression MDR1 CYP450 genes lines A549 treated with cisCarboPt, cisCRu(III) cisDRu(III). ruthenium-based coordinated complexes presented low cytotoxic antiproliferative activities, high IC50 values, 196 (±15.49), 472 (±20.29) 175 (±1.41) cisDRu(III), respectively. tested compounds induced apoptosis cells as evidenced by caspase 3 activation, but only at concentrations. Results also revealed that amplification P-gp gene greater exposed cisCarboPt than Taken together these results strongly demonstrate MDR-1 over-expression could be associated a MDR phenotype moreover, it contributing platinum, structurally-related compound, resistance cells. identification characterization novel mechanisms drug will enable development new generation anti-cancer drugs increase sensitivity and/or represent more effective chemotherapeutic agents.

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