In normal and tumor cells, polyunsaturated fatty acids (PUFAs) act as intracellular second messengers, which play a role in signaling, proliferation and cell death. PUFAs have selective tumoricidal action and may alter sensitivity of tumor cells to cisplatin (CDDP), a commonly used anticancer agent [1-3].

The aim of this study was to evaluate the influence of arachidonic acid (AA, 20:4 n-6), eicosapentaenoic acid (EPA, 20:5 n-3), docosahexaenoic acid (DHA, 22:6 n-3) and CDDP on autophagy and apoptosis in A549 human lung adenocarcinoma cells.

Viability of A549 cellstreated with CDDP and PUFAs was measured using the XTT tetrazolium salt based assay. Caspase-3/7 activity was estimated using ApoTox-Glo kit (Promega). Autophagic vacuoles were detected by Cyto-ID Autophagy Detection Kit (Enzo). The results were compared to control cultures maintained in the absence of CDDP and PUFAs.

PUFAs, in particular EPA and DHA, added to the cultivation medium, increased the antitumour activity of CDDP in A549 cells in a concentration dependent manner. In case of AA this effect was observed at the highest of the concentrations tested only (100mM). Both, EPA and DHA, but not AA significantly increased the amount of autophagic vacuoles and induced caspase-3/7 activity.

The obtained results suggest that the antiproliferative effect of CDDP in A549 cells can be enhanced by AA and in particular by EPA and DHA through their influence on autophagic and apoptotic cell death. It is likely that EPA and DHA incorporated to the tumour cells may improve outcomes in lung cancer patients.

References:

1. Zajdel A, Wilczok A, Gruchlik A, Paduszyński P, Dzierżewicz Z: The expression of genes encoding antioxidant enzymes in lung adenocarcinoma A549 cells exposed to cisplatin supplemented by polyunsaturated fatty acids. Adv Clin Exp Med. 2010; 19(5), 585-591
2. Yao QH, Zhang XC, Fu T, Gu JZ, Wang L, Wang Y, Lai YB, Wang YQ, Guo Y: ω-3 polyunsaturated fatty acids inhibit the proliferation of the lung adenocarcinoma cell line A549 in vitro. Mol Med Rep. 2014; 9(2): 401-406
3. Hajjaji N, Bougnoux P: Selective sensitization of tumors to chemotherapy by marine-derived lipids: a review. Cancer Treat Rev. 2013; 39(5): 473-488

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