We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-
gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale), in
colon cancer cells. The compound was evaluated in two human
colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-
gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-
gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of
phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-
gingerol in SW-480 cells was associated with activation of
caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-
gingerol down-regulated
Phorbol Myristate Acetate (PMA) induced phosphorylation of ERK1/2 and JNK MAP
kinases and activation of
AP-1 transcription factor, but had only little effects on phosphorylation of
p38 MAP kinase and activation of
NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP
kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-
gingerol against
colon cancer.