6-shogaol induces autophagic cell death then triggered apoptosis in colorectal adenocarcinoma HT-29 cells

Biomed Pharmacother. 2017 Sep;93:208-217. doi: 10.1016/j.biopha.2017.06.038. Epub 2017 Jun 20.

Abstract

6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death. After 24h, cell shrinkage and Caspase-3/7 activities rising, suggesting that apoptotic cell death had increased. And after 48h, the result of TUNEL assay indicated the highest occurrence of apoptosis upon 6-shogaol treatment. It appeared that apoptosis is triggered by autophagy in 6-shogaol treated HT-29 cells, the damage of autophagic cell death initiated apoptosis program.

Keywords: 6-shogaol; Apoptosis; Autophagy; Colorectal cancer; HT 29.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Catechols / pharmacology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Ginger / chemistry
  • HT29 Cells
  • Humans
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Catechols
  • Reactive Oxygen Species
  • shogaol
  • Caspase 3
  • Caspase 7