Studies on antitumor mechanism of two planar platinum(II) complexes with 8-hydroxyquinoline: Synthesis, characterization, cytotoxicity, cell cycle and apoptosis

[Pt(Q)(2)] (I) and [Pt(MQ)(2)] (2) exhibited enhanced cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, A549 tumor cells but low cytotoxicity on normal HL-7702 cells. 1 and 2 could cause the cell cycle arrest in G2 and S phase, respectively. While pifithrin-alpha, a specific p53 inhibitor, induced cell cycle arrest in G1 phase. Although 1, 2 and pifithrin-alpha caused serious inhibition on p53,1 and 2 significantly cause the loss of mitochondrial membrane potential and increase of the reactive oxygen species level, cytochrome c, apaf-1 and caspase-3/9 ratio in BEL-7404 cells. 1 and 2 may trigger the cell apoptosis through a mitochondrial dysfunction pathway whereas pifithrin-alpha does not. The interactions of 1 and 2 with DNA are most probably via an intercalation. (C) 2014 Elsevier Masson SAS. All rights reserved.