title: 20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol induces apoptosis via             induction of endoplasmic reticulum stress in human colon cancer cells.
abstract: Previously, we reported that 20-O-(β-D-gluco-pyranosyl)-20(S)-protopanaxadiol             (Compound K, a meta-bolite of ginseng saponin) induces mitochondria-dependent             and caspase-dependent apoptosis in HT-29 human colon cancer cells via the generation             of reactive oxygen species. The aim of the present study was to elucidate the             mechanism underlying apoptosis induced by Compound K with respect to endoplasmic             reticulum (ER) stress in HT-29 cells. In the present study, Compound K induced             apoptotic cell death as confirmed by DNA fragmentation and apoptotic sub-G1 cell             population. Compound K also induced ER stress as indicated by staining with ER             tracker, cytosolic and mitochondrial Ca2+ overloading, phosphorylation of protein-kinase-like             endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation             factor-2α (eIF-2α), phosphorylation of IRE-1, splicing of ER stress-specific X-box             transcription factor-1 (XBP-1), cleavage of activating transcription factor-6             (ATF-6), upregulation of glucose-regulated protein-78 (GRP-78/BiP) and CCAAT/enhancer-binding             protein-homologous protein (CHOP), and cleavage of caspase-12. Furthermore, downregulation             of CHOP expression using siCHOP RNA attenuated Compound K-induced apoptosis. Taken             together, these results support the important role of ER stress response in mediating             Compound K-induced apoptosis in human colon cancer cells.
authors: School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju 690-756, Republic of Korea.
authors: Rui
authors: R
authors: Zhang
authors: Young
authors: Y
authors: Chung
authors: Hee Sun
authors: HS
authors: Kim
authors: Dong Hyun
authors: DH
authors: Kim
authors: Hye Sun
authors: HS
authors: Kim
authors: Weon Young
authors: WY
authors: Chang
authors: Jin Won
authors: JW
authors: Hyun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053454:Caspase 12 / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D005894:Panax / Q000737:chemistry; D000071701:Regulatory Factor X Transcription Factors; D012502:Sapogenins / Q000008:administration & dosage*; D051742:Transcription Factor CHOP / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000071717:X-Box Binding Protein 1
chemical_list: C482402:20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D012502:Sapogenins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP; D053454:Caspase 12