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http://ir.nhri.org.tw/handle/3990099045/11490
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Title: | Opposite regulation of CHOP and GRP78 and synergistic apoptosis induction by selenium yeast and fish Oil via AMPK activation in lung adenocarcinoma cells |
Authors: | Kao, RH;Lai, GM;Chow, JM;Liao, CH;Zheng, YM;Tsai, WL;Hsia, S;Lai, IC;Lee, HL;Chuang, SE;Whang-Peng, J;Yao, CJ |
Contributors: | National Institute of Cancer Research |
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. |
Date: | 2018-10-08 |
Relation: | Nutrients. 2018 Oct 8;10(10):Article number 1458. |
Link to: | http://dx.doi.org/10.3390/nu10101458 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2072-6643&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000448821300124 |
Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85054771169 |
Appears in Collections: | [莊雙恩] 期刊論文 [賴基銘(2004-2008)] 期刊論文
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