Docosahexaenoic acid increases the expression of oxidative stress-induced growth inhibitor 1 through the PI3K/Akt/Nrf2 signaling pathway in breast cancer cells

被引：56

作者：

Tsai, Chia-Han ^{[1
]}

Shen, You-Cheng ^{[2
]}

Chen, Haw-Wen ^{[3
]}

Liu, Kai-Li ^{[1
,4
]}

Chang, Jer-Wei ^{[5
]}

Chen, Pei-Yin ^{[6
]}

Lin, Chen-Yu ^{[1
]}

Yao, Hsien-Tsung ^{[3
]}

Li, Chien-Chun ^{[1
,4
]}

机构：

[1] Chung Shan Med Univ, Dept Nutr, Taichung, Taiwan

[2] Chung Shan Med Univ, Dept Hlth Diet & Ind Management, Taichung, Taiwan

[3] China Med Univ, Dept Nutr, Taichung, Taiwan

[4] Chung Shan Med Univ Hosp, Dept Nutr, Taichung, Taiwan

[5] Natl Hlth Res Inst, Inst Mol & Genom Med, Miaoli, Taiwan

[6] MingDao Univ, Dept Recreat & Holist Wellness, Changhua, Taiwan

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2017年 / 108卷

关键词：

OSGIN1; Docosahexaenoic acid; Nrf2; Apoptosis; Breast cancer; HUMAN ENDOTHELIAL-CELLS; MATRIX-METALLOPROTEINASE-9; EXPRESSION; OXIDIZED PHOSPHOLIPIDS; EICOSAPENTAENOIC ACID; HEME OXYGENASE-1; GENE-EXPRESSION; LINOLEIC-ACID; APOPTOSIS; ACTIVATION; INDUCTION;

D O I：

10.1016/j.fct.2017.08.010

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Oxidative stress-induced growth inhibitor 1 (OSGIN1), a tumor suppressor, inhibits cell proliferation and induces cell death. N-6 and n-3 PUFAs protect against breast cancer, but the molecular mechanisms of this effect are not clear. We investigated the effect of n-6 and n-3 PUFAs on OSGINI expression and whether OSGIN1 is involved in PUFA-induced apoptosis in breast cancer cells. We used 100 mu M of n-6 PUFAs including arachidonic acid, linoleic acid, and gamma-linolenic acid and n-3 PUFAs including alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). Only DHA significantly induced OSGIN1 protein and mRNA expression. DHA triggered reactive oxygen species (ROS) generation and nuclear translocation of Nrf2. LY294002, a PI3K inhibitor, suppressed DHA-induced OSGIN1 protein expression and nuclear accumulation of Nrf2. Nrf2 knockdown attenuated DHA-induced OSGINI expression. N-Acetyl-L-cysteine, a ROS scavenger, abrogated the DHA-induced increases in Akt phosphorylation, Nrf2 nuclear accumulation, and OSGINI expression. DHA induced the Bax/Bcl-2 ratio, mitochondrial accumulation of OSGIN1 and p53, and cytochrome c release; knockdown of OSGINI diminished these effects. In conclusion, induction of OSGINI by DHA is at least partially associated with increased ROS production, which activates PI3K/Akt/Nrf2 signaling. Induction of OSGINI may be involved in DHA-induced apoptosis in breast cancer cells. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：276 / 288

页数：13

共 57 条

[1] Docosahexaenoic acid induces increases in [Ca2+]i via inositol 1,4,5-triphosphate production and activates protein kinase Cγ and -δ via phosphatidylserine binding site:: Implication in apoptosis in U937 cells [J].