ANTICANCER EFFECTS OF HETEROCYCLIC SCHIFF BASE LIGANDS AND THEIR METAL COMPLEXES ON LEUKEMIA CELLS

Abstract

Chemotherapy is one of the most important treatment options in the treatment of all types of leukemia, but multi-drug resistance (MDR) often precludes the success of this treatment. In this study, anticancer properties of heterocyclic salicylaldimines and their Cu(II) complexes on K562 myelomonocytic leukemia cells were investigated. Doxorubicin (DOX) and Etoposide (ETO) were used as positive control. Compounds (C1-8 and DOX, ETO) placed to 96 well culture plate in triplicate order at doses of 1, 10, 100, 1000 µM and then K562 cells were seeded into the wells in doses 105 /ml. After 72 h incubation, colorimetric MTT test was performed to determine IC50 values of each compound. Antiproliferative effects of compounds determined using CFSE assay. Apoptosis induction potential of each compound determined by mitochondrial membrane potential analysis (Rho123), cleaved caspase-3 expression analysis by flow cytometry and immunofluorescent staining and cell morphology analysis by giemza, H&E and PAP protocols. The metal complexes of the compounds had stronger cytotoxic effects and cleaved caspase-3 expression than their ligands. Mitochondrial membrane potential was found at low levels in cells treated with Schiff base compounds and DOX. In the cell morphology analyzes, chromatin condensation and marginalization, changes in the cell membrane, ghost cells and apoptotic bodies were observed as evidence of apoptosis formation. Among the tested heterocyclic Schiff base compounds, the powerful cytotoxic and apoptosis-inducing potential of 1,1,7,7-tetra-methyl-jululidine-N-heptyl-salicylaldimine Cu(II) complex draw attention as promising compounds withal need for further in vitro and in vivo studies.