Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.
Vitamin E succinate (RRR-alpha-tocopheryl succinate, VES), an efficient inducer of apoptosis, acts as a potent agent for cancer therapy. However, the mechanism by which VES mediates the effects are not yet fully understood. Here we studied the effect of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) on VES-induced apoptosis of SGC-7901 human gastric cancer cells. VES caused cytological changes typical of apoptosis, increased ER dilation and cytosolic Ca(2+) concentration. And endogenous ER stress markers, GRP78 and GRP94 were transcriptionally and translationally altered. In response to VES, induction of CHOP, activation of caspase-4 and JNK were observed. Furthermore, VES also triggered activation of UPR components, including RNA-dependent protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), X-box-binding protein 1 (XBP1), and ATF4 in a concentration- and time-dependent manner. Consequently, our results suggest that VES-induced apoptosis is coupled to ER stress and UPR activation in SGC-7901 human gastric cancer cells.
Huang
Xiaoli
X
Department of Nutrition and Food, Harbin Medical University, Harbin, China.
Zhang
Zhihong
Z
Jia
Li
L
Zhao
Yan
Y
Zhang
Xuguang
X
Wu
Kun
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000975:Antioxidants; D017931:DNA Primers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C053387:endoplasmin; D024502:alpha-Tocopherol