Abstract
Nitro-fatty acids (NFAs) are endogenous lipid mediators capable of post-translational modifications of selected regulatory proteins. Here, we investigated the anti-cancerous effects of nitro-oleic acid (NO2OA) and its combination with gamma irradiation on different cancer cell lines. The effects of NO2OA on cell death, cell cycle distribution, or expression of p21 and cyclin D1 proteins were analyzed in cancer (A-549, HT-29 and FaDu) or normal cell lines (HGF, HFF-1). Dose enhancement ratio at 50 % survival fraction (DERIC50) was calculated for samples pre-treated with NO2OA followed by gamma irradiation. NO2OA suppressed viability and induced apoptotic cell death. These effects were cell line specific but not in general selective for cancer cells. HT-29 cell line exerted higher sensitivity toward NO2OA treatment among cancer cell lines tested: induction of cell cycle arrest in the G2/M phase was associated with an increase in p21 and a decrease in cyclin D1 expression. Pre-treatment of HT-29 cells with NO2OA prior irradiation showed a significantly increased DERIC50, demonstrating radiosensitizing effects. In conclusion, NO2OA exhibited potential for combined chemoradiotherapy. Our results encourage the development of new NFAs with improved features for cancer chemoradiation.
Funding source: The Czech Science Foundation
Award Identifier / Grant number: 19-09212S
Acknowledgments
We are grateful to Prof. B. A. Freeman from the Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, USA for providing the NO2OA derivative. We thank M. Travnickova and N. Szamecova for technical assistance with cytotoxicity and clonogenic assays.
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Research ethics: Not applicable.
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Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. Tomas Perecko: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing - original draft; Writing - review & editing. Jana Pereckova: Conceptualization; Investigation; Methodology; Writing - review & editing. Zuzana Hoferova: Investigation; Writing - review & editing. Martin Falk: Funding acquisition; Conceptualization; Supervision; Writing - review & editing.
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Competing interests: The authors state no conflict of interest.
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Research funding: This work was supported by the Czech Science Foundation Grant No. 19-09212S.
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Data availability: The raw data can be obtained on request from the corresponding author.
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