Cellular responses of BRCA1-defective HCC1937 breast cancer cells induced by the antimetastasis ruthenium(II) arene compound RAPTA-T

摘要

An organometallic ruthenium(II) arene compound, Ru((6)-toluene)(PTA)Cl-2 (PTA=1,3,5-triaza-7-phosphaadamantane), termed RAPTA-T, exerts promising antimetastatic properties. In this study, the effects of RAPTA-T on BRCA1-defective HCC1937 breast cancer cells have been investigated, and compared to its effects on BRCA1-competent MCF-7 breast cancer cells. RAPTA-T showed a very low cytotoxicity against both tested cells. Ruthenium is found mostly in the cytoplasmic compartment of both cells. Flow cytometric analysis reveals that the compound arrests the growth of both cells by triggering the G2/M phase that led to the induction of apoptosis. At equimolar concentrations, RAPTA-T causes much more cellular BRCA1 damage in HCC1937 than in MCF-7 cells, suppressing the expression of BRCA1 mRNA in both cell lines with the subsequent down-regulation of the BRCA1 protein. Interestingly, RAPTA-T exhibits an approximately fivefold greater ability to suppress the expression of the BRCA1 protein in HCC1937 than in MCF-7 cells. These data provide insights into the molecular mechanisms by which RAPTA-T exerts its effects on BRCA1-associated breast cancer cells.