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.
Rudra
P K
PK
Institute of Cancer Research and Molecular Biology, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
Krokan
H E
HE
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002283:Carcinoma, Bronchogenic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D004317:Doxorubicin; D005979:Glutathione Peroxidase