title: [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase.
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.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Jeong
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Angelo
authors.initials: A
authors.lastname: Pugliese
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Hong-Gyum
authors.initials: HG
authors.lastname: Kim
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005233:Fatty Alcohols / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D020939:Zingiber officinale; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D000893:Anti-Inflammatory Agents; D002396:Catechols; D005233:Fatty Alcohols; C007845:gingerol; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase