Growth Effects of Some Platinum(II) Complexes with Sulfur-Containing Carrier Ligands on MCF7 Human Breast Cancer Cell Line upon Simultaneous Administration with Taxol

Abstract

The platinum (II)complexes, cis-[PtCl2(CH3SCH2CH2SCH3)] (Pt1), cis-[PtCl2(dmso)2] (dmso is dimethylsulfoxide; Pt2) and cis-[PtCl2(NH3)2] (cisplatin), and taxol (T) have been tested at different equimolar concentrations. Cells were exposed to complexes for 2 h and left to recover in fresh medium for 24, 48 or 72 h. Growth inhibition was measured by tetrazolium WST1 assay Analyses of the cell cycle, and apoptosis were performed by flow cytometry, at the same exposure times. The IC50 value of each platinum(II) complex as well as combination index (CI; platinum(II) complex + taxol) for various cytotoxicity levels were determined by median effects analysis.MCF7 cells were found to be sensitive to both Pt1 and Pt2 complexe These cisplatin analogues influenced the cell growth more effectively as compared to cisplatin. Cytotoxic effect was concentration and time-dependent. Profound growth inhibitory effect was observed for Pt1 complex, across all its concentrations at all recovery periods. A plateau effect was achieved three days after treatment at Pt1 concentrations ≤ 1 μM. Pt2, however, decreased MCF7 cells survival only for the first 24 h ranging between 50-55%. Pt2 cytotoxicity sharply decreased thereafter, approaching 2 h - treatment cytotoxicity level. The median IC50 values for Pt1 and Pt2 were similar (0.337 and 0.3051 μM, respectively) but only for the first 24 h. The IC50 values for Pt1 strongly depend on the recovery period. On simultaneos exposure of cells to taxol and platinum(II) complexes no consistent effect was found. The Cls for combinations of taxol with Pt1 or Pt2 revealed cytotoxic effects that were in most Cases synergistic (Pt1) or less than addtiive (Pt2). Flow cytometry analysis has shown that each platinum(II) complex induced apoptosis in MCF7 cells. The level of apoptosis correlated with cytotoxicity level for the range concentrations. Both cisplatin analogues, at IC50 concentrations, increased the number of MCF7 cells in G0G1 phase of cell cycle. Pt2-treated cells remained arrested in G0G1 phase up to 72 h after treatment. Combination of Pt2 and taxol caused further arrest of cells in G0G1 phase (24 h) in parallel with strong decrement of G2M phase cells.