Crosstalk between endoplasmic reticulum stress and oxidative stress in apoptosis induced by α-tocopheryl succinate in human gastric carcinoma cells

alpha-Tocopheryl succinate (alpha-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 alpha-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 alpha-TOS in SGC-7901 human gastric cancer cells. In response to alpha-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 alpha-TOS transcriptionally and translationally. Furthermore, knocking down CHOP by RNA interference decreased ROS generation, increased glutathione level and induced glutathione peroxidase mRNA expression in alpha-TOS-treated cells, whereas catalase and superoxide dismutases mRNA expression were not altered. The results imply that alpha-TOS induces ER stress response through ROS production, while CHOP perturbs the redox state of SGC-7901 cells treated with alpha-TOS.