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Poster display session

832 - Docosahexaenoic acid mediates susceptible cell death through differential regulation of p62/p-eIF2alpha/NRF2 in LMP1-expressing nasopnaryngeal carcinoma cells

Date

11 Sep 2017

Session

Poster display session

Topics

Cancer Biology

Presenters

Kyu Lim

Citation

Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361

Authors

K. Lim1, K. Jing2, S. Shin3, S. Han4, Y. Yoo4, Y. Jeon4, J. Heo4, G. Kweon4, S. Park5, J. Park5

Author affiliations

  • 1 Dept. Of Biochemistry And Medical Science, Cancer Research Institute,, Chungnam National University College of Medicine, 35015 - Daejeon/KR
  • 2 Stem Cell Research And Cellular Therapy Center, Affiliated Hospital of Guangdong Medical College, 524001 - Zhanjiang/CN
  • 3 Dept. Of Biochemistry And Cancer Research Institute, Chungnam National University College of Medicine, 35015 - Daejeon/KR
  • 4 Dept. Of Biochemistry And Medical Science, Chungnam National University College of Medicine, 35015 - Daejeon/KR
  • 5 Dept.of Biochemistry, Chungnam National University College of Medicine, 35015 - Daejeon/KR
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Resources

Abstract 832

Background

Docosahexaenoic acid (DHA) induces apoptotic cell death through several mechanisms in cancer cells. We have previously demonstrated that DHA triggers apoptosis by increasing reactive oxygen species (ROS) accumulation and the ROS-mediated apoptosis caused by DHA is associated with Nrf2 signaling activation. Here we report that DHA-induced cell death is more susceptible through p62/p-eIF2alpha/NRF2 regulation in LMP-1-expressing nasopharygeal carcinoma (NPC) cells.

Methods

Viability of CNE-LMP1 and HONE-EBV cells was compared with CNE and HONE after DHA treatment by MTT assay. DHA-induced apoptosis was analyzed using the TUNEL assay and Western blot of cleaved form of PARP. Tissue expression of LMP-1 and p62 were observed by immunohistochemistry.

Results

Treatment of four human NPC cells (CNE, CNE-LMP1, HONE, HONE-EBV) with DHA for 24 hr resulted in a dose-dependent inhibition of cell growth. The DHA effect was due to the induction of apoptosis, given that DHA increased the cleaved form of PARP as well as the number of TUNEL-positive cells. The inhibition of CNE-LMP1 and HONE-EBV cells after DHA treatment is more susceptible. compared with CNE and HONE cells without LMP1 by MTT assay. The level of p62 and NRF2 of LMP1-NPC cells were increased after DHA pretreatment cpmpared to control NPC cells. On the other hand, the level of p-eIF2alpha produced reverse result. The activation of Nrf2 signal seems to result from decreased Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1), because DHA remarkably attenuated Keap1 expression levels. Moreover, silencing Nrf2 by small interfering RNAs inhibited the cytotoxic effect of DHA, indicating that Nrf2 activation plays a positive role in the process of DHA-induced apoptosis. Increased staining for LMP1 and p62 was observed in NPC tissues when compared with the nonneplastic (chronic inflammation) tissues.

Conclusions

These results suggest that differential regulation of p62/p-eIF2alpha/NRF2 contributes to susceptible cell death by DHA in LMP-1-expressing NPC cells. Thus, utilization of DHA may represent a promising therapeutic approach for chemoprevention and treatment of human NPC.

Clinical trial identification

Legal entity responsible for the study

Chungnam National University

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2007-0054932, NRF-2015R1D1A1A01056887) and by the framework of international cooperation program This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2007-0054932, NRF-2015R1D1A1A01056887) and by the framework of international cooperation program managed by National Research Foundation of Korea (2015K2A2A6002008)

Disclosure

All authors have declared no conflicts of interest.

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