Cytotoxic copper(ii) salicylaldehyde semicarbazone complexes: Mode of action and proteomic analysis

Abstract

The in vitro cytotoxic studies of a series of salicylaldehyde semicarbazones, HOC6H4CH˭N–NHCONR2 (H2R2) and their Cu(ii) complexes on a number of human tumor cell lines were conducted and it was observed that their cytotoxicities were enhanced following complexation to copper. These copper(ii) complexes also demonstrated higher in vitro activities than the reference drug, cisplatin, on the tumor cell lines at micro molar range. Apoptotic assays and cell cycle analysis of the copper complexes, [Cu(HBnz2)Cl] and [Cu(HBu2)Cl] revealed that they mediated cytotoxicity in MOLT-4 cells via apoptosis. Further proteomic investigation of [Cu(HBnz2)Cl] and [Cu(HBu2)Cl] with respect to their protein expression profiles associated with their mode of action was conducted. By comparing the expression levels of 33 identified protein spots amongst the respective compound-treated profiles, we identified similarities in protein expression patterns between the two copper(ii) complexes. The possible roles of the identified proteins in the execution of apoptosis by these copper(ii) complexes are discussed. The in vitro cytotoxic studies of a series of salicylaldehyde semicarbazones and their Cu(ii) complexes revealed that they mediated cytotoxicity in MOLT-4 cells via apoptosis. Proteomic investigation of some of these complexes was also conducted and their protein expression profiles were obtained.