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Polyunsaturated fatty acids inhibit melanoma cell growth in vitro

Alicja Zajdel , Adam Wilczok , Ewa Chodurek , Arkadiusz R. Gruchlik , Zofia Dzierżewicz

Department of Biopharmacy, Medical University of Silesia, Narcyzów 1, Sosnowiec 41-200, Poland

Abstract

Human malignant melanoma is a highly aggressive and incurable cancer due to intrinsic resistance to apoptosis and reprogramming proliferation and survival pathways during progression. Numerous studies, including our own, linked arachidonic acid (AA, 20:4 n-6), eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) supplementation to induction of apoptosis and decreased proliferation of various cancer cells. The cytotoxic effects result from lipid peroxidation and formation of reactive oxygen species (ROS), which modify proteins, and nucleic acids. DNA damage by ROS causes mutations, and genomic instability leading to uncontrolled proliferation or cell death.
In the present work four human melanoma cell lines differing in origin, doubling time, metastatic potential, and melanin content: A375, A2058, G361, C32 were exposed to AA, EPA or DHA added into culture media in the concentrations ranging from 0 (control) to 100 μM. After 24 h incubation cytotoxicity of the analyzed acids was determined with TOX-2 (In Vitro Toxicology Assay Kit XTT Based, TOX-2, Sigma) test. At the some time oxidative protein modifications were measured using Aldehyde Site (DNA and Protein) Detection Kit (Cayman).
All the acids tested showed marked inhibition of cell proliferation. The observed effects were statistically significant and depended on the concentration. Decrease of proliferation, associated by oxidative protein and DNA damage (measured as aldehyde sites in cells), was observed for EPA and DHA (50 μM and 100 μM) in A375, A2058, and G361 cells. In case of C32 cell line, which is amelanotic melanoma, EPA and DHA inhibited cell proliferation at 100 μM only. The effect of DHA was more pronounced. AA did not show its antiproliferative action in this cell line.

The obtained results suggest that antiproliferative effects of the fatty acids in cultured human melanoma cells depend on the type of acid, its concentration and may be diverse when different melanoma cell lines are used

This work was supported by SUM grant KNW-1-002/P/1/0.

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[2] Siddiqui RA, Harvey K, Stillwell W. Anticancer properties of oxidation products of docosahexaenoic acid. Chem Phys Lipids 2008; 153: 47-56.
[3] Serini S, Piccioni E, Merendino N, Calviello G. Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer. Apoptosis 2009; 14: 135–152.

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Polyunsaturated fatty acids inhibit melanoma cell growth in vitro

Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Arkadiusz R. Gruchlik See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku Submitted: 2012-03-06 11:08 Revised: 2012-03-12 12:46

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

Submitted: 2012-03-06 11:08 Revised: 2012-03-12 12:46