Antitumor activity of Ru(III) complexes carrying beta-diketonato ligands in vitro and in vivo

Abstract

Purpose: To investigate the antitumor activity of two newly synthesized ruthenium(III) [Ru(III)] compounds carrying bidentate ligands: (acac)-acetylacetonate, [Ru(acac)(3)], and (tfac)-trifluoroacetylacetonate [Ru(tfac)(3)]. Materials and methods: The activity of ruthenium(III) analogues was evaluated on HeLa, B16, and Femx cell lines for cytotoxicity in vitro using MTT assay, and inhibition on tumor invading ability in vitro using cell migration and invasion assays, whereas inhibition of tumor growth in vivo was estimated on advanced B16 murine melanoma model. Both compounds were also investigated in combinations with cisplatin, oxaliplatin, or poly ADP-ribose polymerase-1 (PARP-1) inhibitor, in order to determine the pattern of mutual interactions. Results: Applied as single drugs, Ru(tfac)(3) showed high cytotoxic activity against HeLa and Femx cell lines, while Ru(acac)(3) did not reach the IC(50) on any of the cell lines tested. In combinations, Ru(acac)(3) with cisplalin gained synergistic interaction, antagonistic with oxaliplatin, and of different kind with (PARP-1) inhibitor in concentration-and cell line-dependent manner. Ru(acac)(3) exhibited inhibition of HeLa cell migration and gelatinolytic activity of MMP-2 and MMP-9. Ru(tfac)(3) complexes didnot induce significant reduction of melanoma growth in vivo, whereas Ru(acac)(3) did, but the latter failed to contribute in lifespan improvement. Conclusion: The investigated ruthenium complexes showed different levels of antitumor activity in vitro and in vivo, implicating on different mechanisms of their action as well as diverse perspectives in cancer treatment.