Background: A number of Cu(II) chelate complexes that exhibit cytotoxic activity
through cell apoptosis or enzyme inhibition was reported to have numerous biologic
activities including antibacterial, antifungal, antiviral and anti-tumor properties. The
present work aimed to study the effect of new synthesized Cu complex of 4-
azomalononitrile antipyrine [CuL(OH)(ClO4)] which exhibits superoxide dismutase
(SOD)-mimetic activity on tumor in mice induced by Ehrlich ascites carcinoma (EAC)
cell line. Results: The administration of 10 mg/kg body weight [CuL(OH)(ClO4)] 24
hours after intraperitoneal injection of EAC, effectively inhibited tumor growth and
the proliferation of EAC cells. Cu complex ameliorated the increase in serum
aspartate transaminase (AST) and alanine transaminase (ALT) activities after
implantation of EAC cells. On the other hand, the level of creatinine was increased.
Moreover, Cu complex of 4-azomalononitrile antipyrine significantly improved the
hepatic and erythrocytes SOD and GRX activities. The glutathione content of hepatic
tissues and erythrocytes was restored in EAC tumor bearing mice. Furthermore, it
also, inhibited the formation of nitric oxide and lipid peroxidation products
(thiobarbituric acid reactive substance, TBARS) in EAC tumor bearing mice. This
effect was associated with inhibition of cell cycle progression and induction of
apoptosis. Administration of [CuL(OH)(ClO4)] complex 24 hours after injection of
EAC for 3 weeks arrested cells in G0/G1 phase and resulted in a decrease in the
viability. Conclusions: Cu complex [CuL(OH)(ClO4)] has a strong inhibitory activity
against growth of tumors. The anti-tumor mechanism may be mediated by preventing
oxidative damage and induction of apoptosis.