A ginger derivative, zingerone-a phenolic compound-induces ROS-mediated apoptosis in colon cancer cells (HCT-116)

J Biochem Mol Toxicol. 2019 Dec;33(12):e22403. doi: 10.1002/jbt.22403. Epub 2019 Nov 12.

Abstract

Zingerone (ZO), an active phenolic agent derived from Zingiber officinale (Ginger), has many pharmacological properties such as antioxidant, antiangiogenic, and antitumor. However, its potential value in cancer and the mechanism by which ZO wields its therapeutic effects remain obscure. Therefore, in this current study, we explored the effects of ZO on suppressing cell proliferation and enhancing apoptosis in colon cancer cells (HCT116). Our results indicated that ZO significantly enhances the production of reactive oxygen species, lipid peroxidation (thiobarbituric acid reactive substance [TBARS]), and loss of cell viability; and reduces mitochondrial membrane potential and antioxidant levels (SOD, CAT, and GSH) in ZO-treated HCT116 cells in a dose-dependent (2.5, 5, and 10 µM) manner. Furthermore, ZO induces oxidative stress-mediated apoptosis as evidenced by apoptotic morphological changes predicted by AO/EtBr, Hoechst staining and further confirmed by comet assay. Moreover, immunoblotting techniques showed that ZO treatment effectively enhances Bax, caspase-9, and caspase-3 expressions and decreases the expression of Bcl-2 in colon cancer cells. Together, our results evidenced that the antitumor effects of ZO reduce cell proliferation and stimulate apoptosis through modulating pro- and antiapoptotic molecular events in HCT116 colon cancer cells. Therefore, based on our findings, ZO may be used as a therapeutic agent for the treatment of colon cancer.

Keywords: apoptosis; colon cancer; phenolic acid; reactive oxygen species; zingerone.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / pathology*
  • DNA Damage / drug effects
  • Ginger / chemistry*
  • Guaiacol / analogs & derivatives*
  • Guaiacol / pharmacology
  • HCT116 Cells
  • Humans
  • Lipid Peroxidation / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • BAX protein, human
  • BCL2 protein, human
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • zingerone
  • Guaiacol
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9