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

Lipids in Health and Disease

Research

Undurti N Das¹  N Madhavi² 

[1] Jawaharlal Nehru Technological University, 533 003, Kakinada, India;UND Life Sciences, 13800 Fairhill Road, #321, 44120, Shaker Heights, OH, USA;Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering, 530 048, Visakhapatnam, India;UND Life Sciences, 13800 Fairhill Road, #321, 44120, Shaker Heights, OH, USA;

关键词: 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;   

DOI  :  10.1186/1476-511X-10-159

 received in 2011-08-31, accepted in 2011-09-14,  发布年份 2011

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Das and Madhavi; licensee BioMed Central Ltd. 2011