BENZONITRILE/RUTHENIUM(II) COMPLEX INDUCE DNA DAMAGE AND CASPASE-DEPENDENT APOPTOSIS IN HORMONE-NONRESPONSIVE BREAST CANCER CELLS
Francyelli M. S. Mello, Lorena F. Magalhães, Flavia C. Pereira, Wanessa C. Pires, Larissa M. Macedo, Carlos H. de Castro, Alzir A. Batista, Elisângela P. Silveira-Lacerda
BENZONITRILE/RUTHENIUM(II) COMPLEX INDUCE DNA DAMAGE AND CASPASE-DEPENDENT APOPTOSIS IN HORMONE-NONRESPONSIVE BREAST CANCER CELLS
Francyelli M. S. Mello, Lorena F. Magalhães, Flavia C. Pereira, Wanessa C. Pires, Larissa M. Macedo, Carlos H. de Castro, Alzir A. Batista, Elisângela P. Silveira-Lacerda
Institution: Institute of Biological Sciences, UFG, Brazil
“Antimetastatic activities, low toxicity to non-tumor cells and high selectivity for tumor cells make of the ruthenium complexes a promising candidates for development of new chemotherapeutic. This study aimed to determine the cytotoxic, genotoxic, and to elucidate the signaling pathway involved in the death cell process induced by cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (1) and cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (2) in Ehrlich ascites tumor (EAT) cells, in vitro. The cytotoxic and selective potential were evaluated by MTT assay through determination of IC50 values (concentration required for 50% inhibition of cell viability) for EAT cells (murine breast cancer cells) and PBMCs cells (human non-tumor cells). To verify if benzonitrile/ruthenium(II) complexes can induces DNA damage of the EAT cells it was used Comet assay. The IC50 values obtained for EAT and PBMC cells revealed that complex 2 have more cytotoxicity and selectivity for EAT cells than complex 1 and cisplatin. Complex 2 induced DNA damage of the EAT cells at 24 and 48 h post-treatment in all concentrations tested. In consequence, it was observed increase of Tp53 gene expression, G0/G1-arrest cells, and increased levels of cleaved Parp protein. Moreover, the treatment of EAT cells with complex 2 led to an increase in Annexin V-positive cells, induction cell death by caspase 7-mediated apoptosis. Thus, the complex 2 is active and selective for EAT tumor cells, inducing DNA damage, cell cycle arrest and cell death by caspase-dependent apoptosis. Keywords: ruthenium, DNA damage, apoptosis”