MDR1 and cytochrome P450 gene-expression profiles as markers of chemosensitivity in human chronic myelogenous leukemia cells treated with cisplatin and Ru(III) metallocomplexes.

Abstract

Leukemia is a major type of cancer affecting a significant segment of the population, and especially children. In fact, leukemia is the most frequent childhood cancer, with 26% of all cases, and 20% mortality. The multidrug resistance phenotype (MDR) is considered one of the major causes of failure in cancer chemotherapy. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human chronic myelogenous leukemia cells (K-562) treated with cisplatin (cisPt) and two ruthenium-based coordinated complexes [cisCRu(III) and cisDRu(III)]. The tested compounds induced apoptosis in K-562 tumor cells as evidenced by caspase 3 activation. Results also revealed that the amplification of P-gp gene is greater in K-562 cells exposed to cisPt and cisCRu(III) than cisDRu(III). Taken together, all these results strongly demonstrate that MDR-1 overexpression in K-562 cells could be associated to a MDR phenotype, and moreover, it is also contributing to the platinum and structurally related compound, resistance in these cells.