CYTOTOXICITY OF RUTHENIUM/ 2-MERCAPTOPYRIMIDINE COMPLEXES AGAINST BREAST CANCER CELLS

Velozo-Sa VS1, Mello FMS1, Pereira LR2, Lima AP1, Batista AA2 Silveira-Lacerda EP1

Institution: Universidade Federal de Goiás

Among the anticancer agents derived from metals, the most promising are ruthenium compounds for demonstrating anti-metastatic properties, low toxicity to normal cells and high selectivity for tumor cells. In the present study, two ruthenium complexes containing 2-mercaptopyrimidine, DPPM and DPPE, were studied in vitro to determine their biological activity against two breast cancer cells: murine breast carcinoma (Ehrlich tumor), and MDA-MB-231 (ATCC® CRM-HTB-26™) tumor cell line. Furthermore, the selectivity index was determined. The cytotoxicity of ruthenium complexes (DPPM and DPPE) was evaluated by MTT assay. Results demonstrated that the two complexes inhibited the growth of both tumor cell lines. The IC50 values to MDA-MB-231 cells were 0.075 µM (DPPM) and 0.21 µM (DPPE). The IC50 values to Ehrlich cells were 0.24 µM (DPPM) and 0.23 µM (DPPE). Additionally, these compounds showed low cytotoxicity against normal L929 fibroblast cells (0.93 µM for DPPM). Wound healing migration assay was applied. IC50 concentrations were able to inhibit migratory capacity of MDA-MB-231 cells over time on treated cells compared with untreated control cells. This inhibition on cell migration was time and concentration dependent. Clonogenic assay was also performed. Clonogenic assay results with MDA-MB-231 cells treated with DPPM and DPPE (IC50 concentration) had a statistically significant decrease in colony-forming ability compared with untreated cells. To evaluate the type of induced death by DPPM and DPPE, necrosis/apoptosis detection test using propidium iodide and Hoechst 33242 stains by fluorescent microscopy was conducted. After 48 hours of treatment with DPPM and DPPE, morphology of the treated cells showed that most cells underwent cell death by apoptosis, rather than necrosis. Thus, we demonstrated that ruthenium complexes DPPM and DPPE are promising drugs against breast tumor cells, and we will do further investigations about their role as antineoplastic agents for breast cancer.”

Key-words: Breast Cancer, cell death, Ruthenium