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

Abstract

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.

• Authors: P K Rudra, H E Krokan
• Journal: Anticancer research (Anticancer Res) 2001 Jan-Feb Vol. 21 Issue 1A Pg. 29-38 ISSN: 0250-7005 [Print] Greece
• PMID: 11299749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Omega-3
• Docosahexaenoic Acids
• Doxorubicin
• Glutathione Peroxidase

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Carcinoma, Bronchogenic (drug therapy, metabolism, pathology)
• Cell Division (drug effects)
• Docosahexaenoic Acids (pharmacology)
• Doxorubicin (pharmacology)
• Drug Synergism
• Fatty Acids, Omega-3 (metabolism)
• Glioblastoma (drug therapy, metabolism, pathology)
• Glutathione Peroxidase (metabolism)
• Humans
• Lipid Peroxidation (drug effects)
• Tumor Cells, Cultured