title: Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro.
abstract: Previous studies showed that γ-linolenic acid (GLA, 18: 3 ω-6), arachidonic acid (AA, 20:4 ω-6), eicosapentaenoic acid (EPA, 20: 5 ω-3) and docosahexaenoic acid (DHA, 22:6 ω-3) have selective tumoricidal action. In the present study, it was observed that dihomo-gamma-linolenic acid (DGLA) and AA, EPA and DHA have cytotoxic action on both vincristine-sensitive (KB-3-1) and resistant (KB-Ch(R)-8-5) cancer cells in vitro that appeared to be a free-radical dependent process but not due to the formation of prostaglandins, leukotrienes and thromboxanes. Uptake of vincristine and fatty acids was higher while their efflux was lower in KB-3-1 cells compared with KB-Ch(R)-8-5 cells, suggesting that drug resistant cells have an effective efflux pump. GLA, DGLA, AA, EPA and DHA enhanced the uptake and decreased efflux in both drug-sensitive and drug-resistant cells and augmented the susceptibility of tumor cells especially, of drug-resistant cells to the cytotoxic action of vincristine. These results suggest that certain polyunsaturated fatty acids have tumoricidal action and are capable of enhancing the cytotoxic action of anti-cancer drugs specifically, on drug-resistant cells by enhancing drug uptake and reducing its efflux. Thus, polyunsaturated fatty acids either by themselves or in combination with chemotherapeutic drugs have the potential as anti-cancer molecules.
authors.affiliation: Jawaharlal Nehru Technological University, Kakinada-533 003, India. Undurti@hotmail.com
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
authors.forename: N
authors.initials: N
authors.lastname: Madhavi
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009994:Osmolar Concentration; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014750:Vincristine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005609:Free Radicals; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D014750:Vincristine