[6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase.
[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.
Jeong
Chul-Ho
CH
The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Bode
Ann M
AM
Pugliese
Angelo
A
Cho
Yong-Yeon
YY
Kim
Hong-Gyum
HG
Shim
Jung-Hyun
JH
Jeon
Young-Jin
YJ
Li
Honglin
H
Jiang
Hualiang
H
Dong
Zigang
Z
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
D000893:Anti-Inflammatory Agents; D002396:Catechols; D005233:Fatty Alcohols; C007845:gingerol; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase