[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling

Abstract

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.

Lead Phytochemicals for Anticancer Drug Development

“…Genistein, the isoflavone of soybean exerts its anticancer effects via inhibition of NF-κB and Akt signaling pathways (Li et al, 2012). Gingerol targets the Erk1/2/JNK/AP-1 signaling and induces caspase-dependent apoptosis in colon cancer cells (Radhakrishnan et al, 2014). Kaempferol acts on proto-oncogene tyrosine protein kinase (Src), Erk1/2 and Akt pathways in pancreatic cancer cells and retard their growth & migration (Lee and Kim, 2016).…”

Gingerol Inhibits Serum-Induced Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by Suppressing p38 MAPK Activation

“…10 Cells were cultured in DMEM, supplemented with 10% FBS and antibiotics at 37 C in a humidified atmosphere of 95% air and 5% CO 2 incubator. All VSMCs used for experiments were between the third and fifth passages.…”

The Role of 6-Gingerol on Inhibiting Amyloid β Protein-Induced Apoptosis in PC12 Cells

“…15 6-Gingerol, a phenolic compound, is the major gingerol in ginger rhizomes with diverse pharmacological activities, including anti-tumor, anti-inflammatory, and anti-oxidant effects. [16][17][18][19] In a recent study, 6-gingerol exhibited neuroprotective effects against cell apoptosis induced by Ab through its antioxidative role. 20 In this study, we aimed to determine if 6-gingerol exhibited protective effects of 6-gingerol on Ab 1-42 -induced damages and apoptotic death in pheochromocytoma cells (PC12) cells, and not only investigated the role of 6-gingerol in the process of anti-oxidative stress but also proved its role of anti-inflammatory responses and Akt/GSK-3b signaling pathway to investigate the underlying mechanisms by which 6-gingerol may exert its neuroprotective effects.…”