[6]-Gingerol-induced cell cycle arrest, reactive oxygen species generation, and disruption of mitochondrial membrane potential are associated with apoptosis in human gastric cancer (AGS) cells

J Biochem Mol Toxicol. 2018 Oct;32(10):e22206. doi: 10.1002/jbt.22206. Epub 2018 Aug 8.

Abstract

Ginger (Zingiber officinale Roscoe), a monocotyledonous herb, is widely used as an herbal medicine owing to the phytoconstituents it possesses. In the current study, the quantity of [6]-gingerol, the major phenolic ketone, in the fresh ginger and dried ginger rhizome was found to be 6.11 µg/mg and 0.407 µg/mg. Furthermore, [6]-gingerol was assessed for its antiapoptotic effects in human gastric adenocarcinoma (AGS) cells evidenced by acridine orange/ethidium bromide staining technique and Annexin-V assay. An increase in reactive oxygen species (ROS) generation led to a decrease in mitochondrial membrane potential (MMP) and subsequent induction of apoptosis. Results disclose that perturbations in MMP are associated with deregulation of Bax/Bcl-2 ratio at protein level, which leads to upregulation of cytochrome-c triggering the caspase cascade. These enduringly suggest that [6]-gingerol can be effectively used for targeting the mitochondrial energy metabolism to manage gastric cancer cells.

Keywords: [6]-gingerol; apoptosis; gastric cancer; mitochondrial membrane potential (MMP); reactive oxygen species (ROS).

MeSH terms

  • Acridine Orange / chemistry
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Catechols / analysis
  • Catechols / pharmacology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Cytochromes c / metabolism
  • Ethidium / chemistry
  • Fatty Alcohols / analysis
  • Fatty Alcohols / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects*
  • Plant Extracts / chemistry
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Up-Regulation
  • Zingiber officinale / chemistry
  • bcl-2-Associated X Protein / metabolism

Substances

  • Annexin A5
  • BAX protein, human
  • Catechols
  • Fatty Alcohols
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Cytochromes c
  • gingerol
  • Caspases
  • Ethidium
  • Acridine Orange