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

¹The Hormel Institute, University of Minnesota, Austin, Minnesota; ²Department of Pharmacology, College of Medicine, Chosun University, Gwanju, Republic of Korea; ³Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science; and ⁴School of Pharmacy, East China University of Science and Technology, Shanghai, China

^* To whom correspondence should be addressed. E-mail: zgdong{at}hi.umn.edu.

	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]

Key Words: [6]-gingerol, LTA₄H, LTB₄, chemoprevention, colorectal carcinoma, nude mice