Cytotoxic copper(II) salicylaldehyde semicarbazone complexes: mode of action and proteomic analysis
Wan Yen Lee1, Peter Peng Foo Lee, Yaw Kai Yan
1Natural Sciences & Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore, Republic of Singapore. peter.lee@nie.edu.sg
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.
