Diaminobenzene Schiff Base Induces Caspase 9-dependent Apoptosis In U937 Leukemia Cells Diaminobenzene Schiff Base Induces Caspase 9-dependent Apoptosis In U937 Leukemia Cells

Abstract Metal complex Schiff base compounds have been shown to be cytotoxic in vitro. However little is known concerning anticancer activity of Schiff bases that lack metal cations. The antineoplastic properties of two isomeric derivatives of diaminobenzene bis-Schiff base compounds, namely: N,N '-Bis(2-hydroxy-3-methoxybenzylidene)-1,2-diaminobe nzene (2MJ) and N,N '-Bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminobe nzene (2MH) towards U937 and K562 leukemia cell lines were investigated in this study. Both compounds were more cytotoxic towards U937 lymphoma cell with little effect on K562 cells when analysed using Sodium 3′-[1-(phenylamino-carbonyl)-3,4-Tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) cell proliferation assay technique . The IC 50 value for 2MJ was almost half of 2MH . Both compounds were also found to induce apoptosis in U937 leukemia cells as evidenced by the induction of caspase 3 and 7. The level of caspase 3/7 induction was more pronounced in cells treated with 2MJ compared to 2MH. Caspase-9 was identifiedas the regulatory upstream caspase activated in U937 cells treatedwith 2MH and 2MJ, implicating the mitochondrial apoptoticpathway in diaminobenzene Schiff base-induced leukemia cell death. Both agents caused negligible effect on caspase-8 indicating a non Fas ligand receptor involvement in the apoptosis cascade. Neither compounds showed significant mutagenic outcome in the AMES mutagenicity assay. The result of this study highlights the potential of diaminobenzene bis-Schiff base compounds as a prospective agent to target cancer cells via the mitochondria