Shogaol overcomes TRAIL resistance in colon cancer cells via inhibiting of survivin

Tumour Biol. 2015 Nov;36(11):8819-29. doi: 10.1007/s13277-015-3629-2. Epub 2015 Jun 11.

Abstract

In this study, we showed the ability of representative shogaol, which as a major component of ginger, to overcome TRAIL resistance by increasing apoptosis in colon cancer cells. Shogaol increased death receptor 5 (DR5) levels. Furthermore, shogaol decreased the expression level of antiapoptotic proteins (survivin and Bcl-2) and increased pro-apoptotic protein, Bax. Shogaol treatment induced apoptosis and a robust reduction in the levels of the antiapoptotic protein survivin but did not affect the levels of many other apoptosis regulators. Moreover, knockdown of survivin sensitized colon cancer cells to resistant of TRAIL-induced apoptosis. Therefore, we showed the functions of shogaol as a sensitizing agent to induce cell death of TRAIL-resistant colon cancer cells. This study gives rise to the possibility of applying shogaol as an antitumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant colon tumor therapy.

Keywords: Apoptosis; Death receptor 5 (DR5); Shogaol; Survivin; Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Catechols / administration & dosage*
  • Catechols / chemistry
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Synergism
  • Ginger / chemistry
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / genetics*
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics

Substances

  • BAX protein, human
  • BIRC5 protein, human
  • Catechols
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • bcl-2-Associated X Protein
  • shogaol