Back to Search
Start Over
Can tumour cell drug resistance be reversed by essential fatty acids and their metabolites?
Can tumour cell drug resistance be reversed by essential fatty acids and their metabolites?
- Source :
-
Prostaglandins, leukotrienes, and essential fatty acids [Prostaglandins Leukot Essent Fatty Acids] 1998 Jan; Vol. 58 (1), pp. 39-54. - Publication Year :
- 1998
-
Abstract
- Tumour cell drug resistance is a major problem in cancer chemotherapy. Essential fatty acids have been shown to be cytotoxic to a variety of tumour cells in vitro. But, the effect of these fatty acids on tumour cell drug resistance has not been well characterized. Gamma-linolenic acid (GLA) of the n-6 series and eicosapentaenoic acid (EPA) of the n-3 series potentiated the cytotoxicity of anti-cancer drugs: vincristine, cis-platinum and doxorubicin on human cervical carcinoma (HeLa) cells in vitro. Alpha-linolenic acid (ALA), GLA, EPA and docosahexaenoic acid (DHA) enhanced the uptake of vincristine by HeLa cells. In addition, DHA, EPA, GLA and DGLA were found to be cytotoxic to both vincristine-sensitive (KB-3-1) and -resistant (KB-ChR-8-5) human cervical carcinoma cells in vitro. Pre-incubation of vincristine-resistant cells with sub-optimal doses of fatty acids enhanced the cytotoxic action of vincristine. GLA, DGLA, AA, EPA and DHA enhanced the uptake and inhibited the efflux of vincristine and thus, augmented the intracellular concentration of the anti-cancer drug(s). Fatty acid analysis of KB-3-1 and KB-ChR-8-5 cells showed that the latter contained low amounts of ALA, GLA, 22:5 n-3 and DHA in comparison to the vincristine-sensitive cells. The concentrations of GLA and DHA were increased 10-15 fold in the phospholipid, free fatty acid and ether lipid cellular lipid pools of GLA and DHA treated cells. These results coupled with the observation that various fatty acids can alter the activity of cell membrane bound enzymes such as sodium-potassium-ATPase and 5'-nucleotidase, levels of various anti-oxidants, p53 expression and the concentrations of protein kinase C suggest that essential fatty acids and their metabolites can reverse tumour cell drug-resistance at least in vitro.
- Subjects :
- 5'-Nucleotidase metabolism
Antineoplastic Agents pharmacokinetics
Antineoplastic Agents toxicity
Catalase drug effects
Cell Division drug effects
Cell Survival drug effects
Docosahexaenoic Acids pharmacology
Eicosapentaenoic Acid pharmacology
Fatty Acids analysis
Fatty Acids, Essential metabolism
Fatty Acids, Essential toxicity
Linolenic Acids pharmacology
Lipids analysis
Membrane Proteins metabolism
Protein Kinase C metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Superoxide Dismutase drug effects
Tumor Cells, Cultured
Vincristine pharmacology
Vincristine toxicity
Drug Resistance physiology
Fatty Acids, Essential pharmacology
Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0952-3278
- Volume :
- 58
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Prostaglandins, leukotrienes, and essential fatty acids
- Publication Type :
- Academic Journal
- Accession number :
- 9482165
- Full Text :
- https://doi.org/10.1016/s0952-3278(98)90128-4