6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression

Mol Nutr Food Res. 2008 May;52(5):527-37. doi: 10.1002/mnfr.200700157.


Ginger, the rhizome of Zingiber officinale, is a traditional medicine with anti-inflammatory and anticarcinogenic properties. This study examined the growth inhibitory effects of the structurally related compounds 6-gingerol and 6-shogaol on human cancer cells. 6-Shogaol [1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one] inhibits the growth of human cancer cells and induces apoptosis in COLO 205 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in the early stages of 6-shogaol-induced apoptosis, preceding cytochrome c release, caspase activation, and DNA fragmentation. Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Catechols / isolation & purification
  • Catechols / pharmacology*
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology
  • Colorectal Neoplasms / pathology*
  • Fatty Alcohols / isolation & purification
  • Fatty Alcohols / pharmacology
  • Ginger
  • Humans
  • Membrane Potentials / drug effects
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / physiology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • RNA, Neoplasm / drug effects
  • RNA, Neoplasm / isolation & purification
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor CHOP / drug effects
  • Transcription Factor CHOP / genetics


  • Catechols
  • DDIT3 protein, human
  • Fatty Alcohols
  • Plant Extracts
  • RNA, Neoplasm
  • Reactive Oxygen Species
  • Transcription Factor CHOP
  • shogaol
  • gingerol
  • Caspases