Background: The RAPTA-EA1 complex [ruthenium(II)-arene 1,3,5-triaza-7-phosphaadamantane (pta)
complex with an arene-tethered ethacrynic acid ligand] has been reported to overcome drug resistance that developed
due to the current use of platinum-based treatments. However, the exact mechanism of action of RAPTA-EA1 remains
largely unexplored and unknown.
Objective: Here we have further studied the effect of RAPTA-EA1 on BRCA1-defective HCC1937 breast cancer cells
and compared its effects on BRCA1-competent MCF-7 breast cancer cells.
Method: HCC1937 and MCF-7 breast cancer cells were treated with the RAPTA-EA1 complex. The cytotoxicity of
ruthenium-induced cells was evaluated by a MTT assay. Cellular uptake of ruthenium was determined by ICP-MS.
Cell cycle and apoptosis were assessed using a flow cytometer. Expression of BRCA1 mRNA and its encoded protein
was quantitated by a real-time RT-PCR and Western blotting.
Results: Differences in cytotoxicity were correlated with the differential accumulations of ruthenium and the induction
of apoptosis. The ruthenium complex caused dramatically more damage to the BRCA1 gene in the BRCA1-defective
HCC1937 cells than to the BRCA1-competent MCF-7 cells. It decreased the expression of BRCA1 mRNA in the
BRCA1-competent cells, while in contrast, its expression increased in the BRCA1-defective cells. However, the
expression of the BRCA1 protein was significantly reduced in both types of breast cancer cells.
Conclusion: The results presented here have demonstrated a differential cellular response for the BRCA1-defective and
BRCA1-competent breast cancer cells to RAPTA-EA1. These findings have provided more insight into the actions and
development of the ruthenium-based compounds for use for the treatment of breast cancer.