Cell-specific enhancement of doxorubicin toxicity in human tumour cells by docosahexaenoic acid.

We examined the cytotoxicity of doxorubicin alone, or in combination with docosahexaenoic acid (22:6 n-3), in glioblastoma cell lines A-172 and U-87 MG and bronchial carcinoma cell lines A-427 and SK-LU-1. For both glioblastoma cell lines we found an enhanced cytotoxicity of doxorubicin when given with concentrations of docosahexaenoic acid that alone are non-toxic. In SK-LU-1 cells no such enhancement was observed, whereas a small increase was observed for A-427 cells. The enhanced cytotoxicity in glioblastoma cells was not caused by lipid peroxidation products. In A-427 cells, however, the modest potentiation could be explained by the formation of cytotoxic lipid peroxidation products. Se-glutathione peroxidase activity increased after doxorubicin exposure and even more after addition of Na-selenite, but this did not reduce the cytotoxicity of doxorubicin. These results demonstrated that the mechanisms of enhancement of cytotoxicity by docosahexaenoic acid are complex and cell-specific and do not require increased lipid peroxidation.