Lipids in Health and Disease

official impact factor 2.24

Open Access Research

Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro

Undurti N Das1,2,3* and N Madhavi2

Author Affiliations

1 Jawaharlal Nehru Technological University, Kakinada-533 003, India

2 UND Life Sciences, 13800 Fairhill Road, #321, Shaker Heights, OH 44120, USA

3 Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering, Visakhapatnam-530 048, India

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Lipids in Health and Disease 2011, 10:159 doi:10.1186/1476-511X-10-159

Published: 14 September 2011

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-ChR-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-ChR-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.

Keywords:
Polyunsaturated fatty acids; essential fatty acids; free radicals; vincristine; lipid peroxidation; cancer; uptake; efflux; arachidonic acid; eicosapentaenoic acid; docosahexaenoic acid; gamma-linolenic acid; linoleic acid; linolenic acid