Crosstalk between endoplasmic reticulum stress and oxidative stress in apoptosis induced by α-tocopheryl succinate in human gastric carcinoma cells.
α-Tocopheryl succinate (α-TOS) has been shown to be a potent apoptosis inducer and growth inhibitor in a variety of cancer cells. Our previous studies showed the important role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the apoptosis induced by α-TOS. However, the relationship of oxidative stress with ER stress is still controversial. The objective of the present study was to investigate the interplay between the two stress responses induced by α-TOS in SGC-7901 human gastric cancer cells. In response to α-TOS, cytological changes typical of apoptosis, induction of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein transcription factor (CHOP), and activation of caspase-4 were observed. And the antioxidant N-acetyl-l-cysteine inhibited induction of both GRP78 and CHOP by α-TOS transcriptionally and translationally. Furthermore, knocking down CHOP by RNA interference decreased ROS generation, increased glutathione level and induced glutathione peroxidase mRNA expression in α-TOS-treated cells, whereas catalase and superoxide dismutases mRNA expression were not altered. The results imply that α-TOS induces ER stress response through ROS production, while CHOP perturbs the redox state of SGC-7901 cells treated with α-TOS.
Department of Nutrition and Food Hygiene, Harbin Medical University, 157 Baojian Road, Harbin 150081, People's Republic of China.
Xiaoli
X
Huang
The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Li
L
Li
The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Linyou
L
Zhang
Department of Nutrition and Food Hygiene, Harbin Medical University, 157 Baojian Road, Harbin 150081, People's Republic of China.
Zhihong
Z
Zhang
Department of Nutrition and Food Hygiene, Harbin Medical University, 157 Baojian Road, Harbin 150081, People's Republic of China.
Xiaolin
X
Wang
Department of Nutrition and Food Hygiene, Harbin Medical University, 157 Baojian Road, Harbin 150081, People's Republic of China.
Xuguang
X
Zhang
Department of Nutrition and Food Hygiene, Harbin Medical University, 157 Baojian Road, Harbin 150081, People's Republic of China.
Liying
L
Hou
Department of Nutrition and Food Hygiene, Harbin Medical University, 157 Baojian Road, Harbin 150081, People's Republic of China.
Kun
K
Wu
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D053471:Caspases, Initiator / Q000378:metabolism; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C093516:CASP4 protein, human; D053471:Caspases, Initiator; D005978:Glutathione; D024502:alpha-Tocopherol