Rapid induction of apoptosis in tumor cells treated with a new platinum(II) complex based on amino-thiazolidinone

Abstract

Thiazolidinone derivatives have been previously shown significant anti-cancer activities. Two amino-thiazolidinone complexes, [Pt(HTone)Cl] (1) and [Cu(HTone)Cl] (3) (HTone = (Z)-2-((E)-(1-(pyridin-2-yl)ethylidene)hydrazono)thiazolidin-4-one) and one ethyl-modified [Pt(ETone)Cl₂] (2) (ETone = (Z)-3-ethyl-2-((E)-(1-(pyridin-2-yl)ethylidene) hydrazono)thiazolidin-4-one)], were designed and synthesized in order to explore novel metal-based antitumor agents. MTT assay indicated that 1 and 3 were markedly cytotoxic to MCF-7, HepG-2 and NCI-H460 tumor cells, superior to both cisplatin and the HTone ligand. Massive dead cells were observed as early as 6 h when treated with 1, indicating rapid action of 1 as compared to that of other compounds. More interestingly, Hoechst 33342 staining and flow cytometry analysis illustrated that only complex 1 could induce obvious cell apoptosis within 12 h, which was associated with the high-expression of Bax and cleavage of caspase-3 from 35 kDa to 17 kDa. By means of ICP-MS assay, we found complex 1 could largely accumulate in tumor cells in a short time. Additionally, complex 1 showed no cross resistance against the cisplatin-resistant cells.

Keywords: Amino-thiazolidinone; Cisplatin resistance; Platinum(II) complexes; Pt/Cu uptake; Rapid apoptosis.