Abstract
Previously, we reported that 20-O-(β-D-glucopyranosyl)- 20(S)-protopanaxadiol (Compound K, a metabolite 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-2a (eIF-2a), 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.
Original language | English |
---|---|
Pages (from-to) | 1365-1370 |
Number of pages | 6 |
Journal | Oncology Reports |
Volume | 29 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2013 |
Keywords
- Apoptosis
- CCAAT/enhancer-binding protein-homologous protein
- Compound K
- Endoplasmic reticulum stress