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.
Highlights
Chemoprevention by plant-derived compounds or dietary phytochemicals has emerged as an accessible and promising approach to cancer control and management (1)
Based on the finding that leukotriene A4 hydrolase (LTA4H) is highly expressed in HCT116 cells, we investigated the function of LTA4H in the growth of this cell line
Our results revealed that the knockdown of LTA4H in HCT116 cells by small hairpin RNA (shRNA) (KD1 or KD2) resulted in fewer colonies being formed in soft agar compared with control cells (Fig. 2D)
Summary
Chemoprevention by plant-derived compounds or dietary phytochemicals has emerged as an accessible and promising approach to cancer control and management (1). Despite its anticancer activity against several human cancers, the exact molecular mechanism by which [6]-gingerol exerts its chemopreventive effects is not fully understood. Identification of molecular and cellular targets, which are associated with the suppression of cell malignancy, is important in the prevention of cancer and will provide a better understanding of anticancer mechanisms. Our findings showed that [6]-gingerol suppresses tumor growth of HCT116 cells implanted in nude mice by inhibiting the enzymatic activity of LTA4H. These data indicate that LTA4H might be a highly desirable target for the prevention of colorectal cancers
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