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Nutrients 2018, 10(10), 1458; https://doi.org/10.3390/nu10101458

Opposite Regulation of CHOP and GRP78 and Synergistic Apoptosis Induction by Selenium Yeast and Fish Oil via AMPK Activation in Lung Adenocarcinoma Cells

1
Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
2
Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
3
Taipei Cancer Center, Taipei Medical University, Taipei 11031, Taiwan
4
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
5
National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan
6
Taiwan Nutraceutical Association, Taipei 10596, Taiwan
7
Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
8
Department of Radiation Oncology, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 1 August 2018 / Revised: 18 September 2018 / Accepted: 26 September 2018 / Published: 8 October 2018
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Abstract

Selenium has been intensively studied for the use of cancer prevention and treatment. However, the clinical effects are still plausible. To enhance its efficacy, a combinational study of selenium yeast (SY) and fish oil (FO) was performed in A549, CL1-0, H1299, HCC827 lung adenocarcinoma (LADC) cells to investigate the enhancement in apoptosis induction and underlying mechanism. By sulforhodamine B staining, Western blot and flow cytometric assays, we found a synergism between SY and FO in growth inhibition and apoptosis induction of LADC cells. In contrast, the fetal lung fibroblast cells (MRC-5) were unsusceptible to this combination effect. FO synergized SY-induced apoptosis of A549 cells, accompanied with synergistic activation of AMP-activated protein kinase (AMPK) and reduction of Cyclooxygenase (COX)-2 and β-catenin. Particularly, combining with FO not only enhanced the SY-elevated proapoptotic endoplasmic reticulum (ER) stress marker CCAAT/enhancer-binding protein homologous protein (CHOP), but also reduced the cytoprotective glucose regulated protein of molecular weight 78 kDa (GRP78). Consequently, the CHOP downstream targets such as phospho-JNK and death receptor 5 were also elevated, along with the cleavage of caspase-8, -3, and the ER stress-related caspase-4. Accordingly, inhibition of AMPK by compound C diminished the synergistic apoptosis induction, and elevated CHOP/GRP78 ratio by SY combined with FO. The AMPK-dependent synergism suggests the combination of SY and FO for chemoprevention and integrative treatment of LADC. View Full-Text
Keywords: selenium; fish oil; lung adenocarcinoma; ER stress; apoptosis selenium; fish oil; lung adenocarcinoma; ER stress; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kao, R.-H.; Lai, G.-M.; Chow, J.-M.; Liao, C.-H.; Zheng, Y.-M.; Tsai, W.-L.; Hsia, S.; Lai, I.-C.; Lee, H.-L.; Chuang, S.-E.; Whang-Peng, J.; Yao, C.-J. Opposite Regulation of CHOP and GRP78 and Synergistic Apoptosis Induction by Selenium Yeast and Fish Oil via AMPK Activation in Lung Adenocarcinoma Cells. Nutrients 2018, 10, 1458.

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