Abstract 2872: Mechanism of anti-proliferative and anti-invasive actions of ω3-polyunsaturated fatty acids in human hypopharyngeal carcinoma cells

Abstract

Abstract Hypopharyngeal carcinoma is one of head and neck cancers. According to the latest statistics from the United States National Cancer Institute, it is estimated that about 17,000 Americans will be diagnosed with pharyngeal cancer in 2017. Although ω3-polyunsaturated fatty acids (ω3-PUFAs) have anti-tumorigenic properties in the several cancers, the anti-cancer effect of ω3-PUFAs on hypopharyngeal carcinoma has been not known yet. In this study, we report inhibitory mechanisms of ω3-PUFAs on cell growth and invasion in hypopharyngeal carcinoma. DHA and EPA inhibited the cell growth of FaDu and SNU1041 in a dose- and time-dependent manner; in contrast, arachidonic acid, a ω6-PUFA, had no significant effect. In flow cytometry analysis, subG1 population increased in DHA-treated FaDu and SNU1041. Moreover, apoptotic cell death was confirmed by TUNEL assay, and the induction of cleaved PARP and caspase-3. Furthermore, treatment of hypopharyngeal carcinoma cells with DHA resulted in a significant increase in autophagic activity, as revealed by increased LC3-II levels, GFP-LC3 puncta, and autophagic flux activation. EGF-induced phosphorylation of EGFR, which is frequently overexpressed in hypopharyngeal carcinoma, was also suppressed after DHA pretreatment, and levels of p-Akt (p- Aktthr308 and AktSer473), which is a downstream signal, was also inhibited in the FaDu and SNU1041 cells. The invasiveness of cells was significantly inhibited by DHA treatment in vitro transwell assay as well. The MMP-2 and MMP-9 promoter activities were inhibited after DHA treatment. Cox-2 and VEGF promoter activities were also suppressed by DHA. Furthermore, DHA decreased the levels of reporter activity of NF-κB, which is transcription factor that regulates MMPs, Cox-2 and VEGF expression. Fat1-stably expressing FaDu cells (fFaDu-sc) was established (fFaDu-sc express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously), and the proliferation of fFaDu-sc was more attenuated than that of cells expressing control vectors (fFaDu-cc). Moreover, fFaDu-sc showed reduction of cell invasion compared with fFaDu-cc. in transwell chamber. The MMPs promoter activities were also suppressed in fFaDu-sc. Taken together, these findings provide evidence that ω3-PUFAs may inhibit invasion as well as cell growth through suppression of p-EGFR and MMPs expression in hypopharyngeal carcinoma cells, indicating that the utilization of ω3-PUFAs may represent a potential effective therapy for the chemoprevention and treatment of human hypopharyngeal carcinoma. [This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2015R1D1A1A01056887) and by the framework of international cooperation program managed by National Research Foundation of Korea (2015K2A2A6002008)]. Citation Format: Seung-Hyeon Han, Soyeon Shin, Young-Joo Jeon, Jun-Young Heo, Gi-Ryang Kweon, Seung-Kiel Park, Jong-Il Park, Kyu Lim. Mechanism of anti-proliferative and anti-invasive actions of ω3-polyunsaturated fatty acids in human hypopharyngeal carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2872.