Polyunsaturated fatty acids potentiate cytotoxicity of cisplatin in A549 cells.
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. 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 cells treated 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 vac- uoles 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 antitumor 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 (100 μM). 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 BPA and DHA incorporated to the tumor cells may improve outcomes in lung cancer patients.
Alicja
A
Zajdel
Adam
A
Wilczok
Małgorzata
M
Latocha
Michał
M
Tarkowski
Mirosława
M
Kokocińska
Zofia
Z
Dzierzewicz
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans
D000970:Antineoplastic Agents; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D002945:Cisplatin