[6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase

Cancer Res. 2009 Jul 1;69(13):5584-91. doi: 10.1158/0008-5472.CAN-09-0491. Epub 2009 Jun 16.

Abstract

[6]-Gingerol, a natural component of ginger, exhibits anti-inflammatory and antitumorigenic activities. Despite its potential efficacy in cancer, the mechanism by which [6]-gingerol exerts its chemopreventive effects remains elusive. The leukotriene A(4) hydrolase (LTA(4)H) protein is regarded as a relevant target for cancer therapy. Our in silico prediction using a reverse-docking approach revealed that LTA(4)H might be a potential target of [6]-gingerol. We supported our prediction by showing that [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA(4)H activity in HCT116 colorectal cancer cells. We showed that [6]-gingerol effectively suppressed tumor growth in vivo in nude mice, an effect that was mediated by inhibition of LTA(4)H activity. Collectively, these findings indicate a crucial role of LTA(4)H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA(4)H for the prevention of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Catechols / pharmacology
  • Catechols / therapeutic use*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / prevention & control*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control*
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Epoxide Hydrolases / chemistry
  • Fatty Alcohols / pharmacology
  • Fatty Alcohols / therapeutic use*
  • Female
  • Ginger
  • HCT116 Cells / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Protein Conformation

Substances

  • Anti-Inflammatory Agents
  • Catechols
  • Fatty Alcohols
  • gingerol
  • Epoxide Hydrolases
  • leukotriene A4 hydrolase