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

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

Requests for reprints: Zigang Dong, University of Minnesota, 801 16th Avenue Northeast, Austin, MN 55912-3679. Phone: 507-437-9600; Fax: 507-437-9606; E-mail: zgdong{at}hi.umn.edu.

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

[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]