20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol induces apoptosis via induction of endoplasmic reticulum stress in human colon cancer cells

Rui Zhang, Young Chung, Hee Sun Kim, Dong Hyun Kim, Hye Sun Kim, Weon Young Chang, Jin Won Hyun

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 languageEnglish
Pages (from-to)1365-1370
Number of pages6
JournalOncology Reports
Volume29
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Apoptosis
  • CCAAT/enhancer-binding protein-homologous protein
  • Compound K
  • Endoplasmic reticulum stress

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