European Journal of Medicinal Chemistry 2015-03-06

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

Qi-Pin Qin, Zhen-Feng Chen, Jiao-Lan Qin, Xiao-Ju He, Yu-Lan Li, Yan-Cheng Liu, Ke-Bin Huang, Hong Liang

Index: Eur. J. Med. Chem. 92 , 302-13, (2015)

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Abstract

[Pt(Q)2] (1) 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-α, a specific p53 inhibitor, induced cell cycle arrest in G1 phase. Although 1, 2 and pifithrin-α 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-α does not. The interactions of 1 and 2 with DNA are most probably via an intercalation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.