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Polyunsaturated fatty acids alter expression of genes encoding antioxidant enzymes in A549 cells exposed to doxorubicin

Alicja Zajdel 1,  Piotr Paduszyński 1,  Arkadiusz R. Gruchlik 1,  Joanna Głogowska-Ligus 2,  Adam Wilczok 1,  Zofia Dzierżewicz 1

1. Medical University of Silesia, Department of Biopharmacy, Narcyzow 1, Sosnowiec 41-200, Poland
2. Medical University of Silesia, Department of Epidemiology, Piekarska 18, Bytom 41-902, Poland

Abstract
         Docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5, n-3) exert selective cytotoxicity against various types of cancer cells and inhibit or reverse anticancer drug resistance [1]. Their cytotoxic effect results from lipid peroxidation and formation of free radicals [2]. Anthracycline drugs, such as doxorubicin (DX), work by generating free radicals and therefore may interfere with intracellular antioxidant enzyme system, which is involved in the development of tumor cells resistance [1, 3]. The loss of antioxidant response to oxidative stress in transformed cells may account for the ability of peroxidizable targets such as EPA, DHA to enhance tumor sensitivity to reactive oxygen species generating anticancer drugs.
         The present study was aimed at evaluating of genes expression of superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase (CAT), phospholipid hydroperoxide glutathione peroxidase (GPx-4), and glutathione S-transferase pi (GST-pi) in human lung adenocarcinoma cells (A549) treated with doxorubicin and supplemented with EPA or DHA.
         Viability of A549 cells treated with DX was measured using the XTT tetrazolium salt based assay. Expression of genes encoding the antioxidant enzymes was determined by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) analysis after RNA isolation from A549 cells.
         EPA and DHA added to the cultivation medium, increased the antitumor activity of doxorubicin in these cells in a concentration dependent manner. Both, EPA and DHA downregulated SOD1, SOD2, GPx, and GST-pi genes expression in DX treated A549 cells. The observed changes in mRNA levels of CAT were not statistically significant.
         The results showed that A549 cells are highly susceptible to EPA and DHA. The altered antioxidant enzymes expression correlated with the sensitization of these cells to the cytotoxic effect of doxorubicin. EPA and DHA incorporated to the tumor cells may serve as possible anticancer therapeutic agents or potential adjuvants to chemotherapy.

[1] Vibet S, Goupille C, Bougnoux P, Steghens JP, Goré J, Mahéo K. Sensitization by docosahexaenoic acid (DHA) of breast cancer cells to anthracyclines through loss of glutathione peroxidase (GPx1) response. Free Radic Biol Med 2008; 44: 1483-91.
[2] Siddiqui RA, Harvey K, Stillwell W. Anticancer properties of oxidation products of docosahexaenoic acid. Chem Phys Lipids 2008; 153: 47-56.
[3] Ozkan A, Fiskin K. Protective effect of antioxidant enzymes against drug cytotoxicity in MCF-7 cells. Exp Oncol 2006; 28: 86–88.

 

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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Arkadiusz R. Gruchlik
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-11 15:03
Revised:   2010-03-11 15:07