Effect of 17-oxo-DHA alone and in combination with gemcitabine on lung cancer cell growth

17-oxo-DHA is an endogenous anti-oxidant and anti-inflammatory electrophilic derivative of docosahexaenoic acid (DHA) omega-3 fatty acid. An antitumoral activity for DHA, alone or in combination with standard chemotherapy, was observed in animal models, in clinical studies and in "in vitro" studies. We hypothesized that 17-oxo-DHA might transduce, at least in part, the antitumoral effects of DHA. The aim of the present study was to evaluate the effects of externally supplemented 17-oxo-DHA on the growth and chemosensitivity of lung cancer cells. A panel of histologically different human NSCLC cell lines (SK-MES-1, CALU-1, COLO699, A549, and COR-L23) was used. Cells were treated with or without the 17-oxo-DHA and the anticancer drug gemcitabine, alone or combined. Apoptosis was evaluated by flow cytometry on the basis of Annexin V binding and cell proliferation by a clonogenic assay. 17-oxo-DHA (50 µM, for 72 hrs) significantly increased the apoptosis and enhanced the proapoptotic effect of gemcitabine in all NSCLC cell lines. 17-oxo-DHA (50 µM, for 72 hrs) significantly reduced the proliferation and enhanced the antiproliferative effect of gemcitabine in all NSCLC cell lines. In conclusion, the combination of 17-oxo-DHA with gemcitabine results in an increased inhibitory effect on the NSCLC cell line growth. This indicates that 17-oxo-DHA is an potential therapeutic compound for the development of improved approaches for lung cancer treatment