Opposite regulation of CHOP and GRP78 and synergistic apoptosis induction by selenium yeast and fish oil via AMPK activation in lung adenocarcinoma cells

Ruey Ho Kao, Gi Ming Lai, Jyh Ming Chow, Chien Huang Liao, Yu Mei Zheng, Wei Lun Tsai, Simon Hsia, I. Chun Lai, Hsin Lun Lee, Shuang En Chuang, Jacqueline Whang-Peng, Chih Jung Yao

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1458
JournalNutrients
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 8 2018

Fingerprint

AMP-activated protein kinase
AMP-Activated Protein Kinases
Fish Oils
Selenium
adenocarcinoma
fish oils
selenium
apoptosis
Yeasts
lungs
Apoptosis
yeasts
cells
Endoplasmic Reticulum Stress
synergism
lissamine rhodamine B
endoplasmic reticulum
caspase-4
TNF-Related Apoptosis-Inducing Ligand Receptors
CCAAT-Enhancer-Binding Proteins

Keywords

  • Apoptosis
  • ER stress
  • Fish oil
  • Lung adenocarcinoma
  • Selenium

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Opposite regulation of CHOP and GRP78 and synergistic apoptosis induction by selenium yeast and fish oil via AMPK activation in lung adenocarcinoma cells. / Kao, Ruey Ho; Lai, Gi Ming; Chow, Jyh Ming; Liao, Chien Huang; Zheng, Yu Mei; Tsai, Wei Lun; Hsia, Simon; Lai, I. Chun; Lee, Hsin Lun; Chuang, Shuang En; Whang-Peng, Jacqueline; Yao, Chih Jung.

In: Nutrients, Vol. 10, No. 10, 1458, 08.10.2018.

Research output: Contribution to journalArticle

Kao, Ruey Ho ; Lai, Gi Ming ; Chow, Jyh Ming ; Liao, Chien Huang ; Zheng, Yu Mei ; Tsai, Wei Lun ; Hsia, Simon ; Lai, I. Chun ; Lee, Hsin Lun ; Chuang, Shuang En ; Whang-Peng, Jacqueline ; Yao, Chih Jung. / Opposite regulation of CHOP and GRP78 and synergistic apoptosis induction by selenium yeast and fish oil via AMPK activation in lung adenocarcinoma cells. In: Nutrients. 2018 ; Vol. 10, No. 10.
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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.",
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T1 - Opposite regulation of CHOP and GRP78 and synergistic apoptosis induction by selenium yeast and fish oil via AMPK activation in lung adenocarcinoma cells

AU - Kao, Ruey Ho

AU - Lai, Gi Ming

AU - Chow, Jyh Ming

AU - Liao, Chien Huang

AU - Zheng, Yu Mei

AU - Tsai, Wei Lun

AU - Hsia, Simon

AU - Lai, I. Chun

AU - Lee, Hsin Lun

AU - Chuang, Shuang En

AU - Whang-Peng, Jacqueline

AU - Yao, Chih Jung

PY - 2018/10/8

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AB - 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.

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