IN VITRO EFFECTS OF DOXORUBICIN AND DERACOXIB ON OXIDATIVE-STRESS-RELATED PARAMETERS IN CANINE MAMMARY CARCINOMA CELLS

Abstract

The present study evaluated the effects of doxorubicin (DOX) and deracoxib (DER), as single agents and in combination treatments, on antioxidant parameters in the canine mammary carcinoma cell line CMT-U27. The cells were exposed to DOX and DER for 24, 48 and 72 h. The viability and malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and total glutathione (GSH) activities of CMT-U27 cells were determined. The half inhibition concentration (IC50) of DOX was found to be similar to 0.9 mu M in the 72-h period. IC50 and 1/10 IC50 concentrations of DOX were combined with all concentrations of DER (50-1000 mu M) in the combination experiments. The results showed increased oxidative status associated with significant decreases of CAT and GSH levels in CMT-U27 cells exposed to 10-mu M and higher concentrations of DOX compared to control cells. In contrast, there were no significant changes in the groups tested with any of the concentrations of DER (50-1000 mu M). In combination treatments, DER attenuated DOX-induced oxidative damage by modulating the enzymatic and non-enzymatic components in CMT-U27 cells. We suggest that the combination of DOX and DER can be beneficial in the treatment of cancer cells by increasing cellular responses to oxidative stress. In conclusion, the use of COX inhibitor in conjunction with a chemotherapeutic agent may provide a basis for new concepts of cancer treatment through systematic modulation of the antioxidant defence systems in mammary cancers of animals.