[6]-Gingerol Suppresses Colon Cancer Growth by Targeting Leukotriene A4 Hydrolase

Abstract

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 A4 hydrolase (LTA4H) protein is regarded as a relevant target for cancer therapy. Our in silico prediction using a reverse-docking approach revealed that LTA4H 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 LTA4H 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 LTA4H activity. Collectively, these findings indicate a crucial role of LTA4H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA4H for the prevention of colorectal cancer. [Cancer Res 2009;69(13):5584–91]