6‐Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase‐9 expression via blockade of nuclear factor‐κB activation

Abstract

BACKGROUND AND PURPOSEShogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms. EXPERIMENTAL APPROACHThe anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-kB (NF-kB) activation were further determined. KEY RESULTSShogaols (6-, 8-and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-kB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IkB phosphorylation and degradation that subsequently led to suppression of NF-kB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resulting reduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-kB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation. CONCLUSIONS AND IMPLICATIONS6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-kB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments. AbbreviationsAP-1, activator protein-1; ECM, extracellular matrix; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IKK, IkB kinase; IkBa, inhibitor of kBa; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; NF-kB, nuclear factor-kB; PMA, phorbol 12-myristate 13-acetate BJP British Journal of Pharmacology

Hispolon inhibits TPA-induced invasion by reducing MMP-9 expression through the NF-κB signaling pathway in MDA-MB-231 human breast cancer cells

“…The present study also indicated that hispolon suppressed the secretion and expression of MMP-9 in a dose-dependent manner in TPA-induced MDA-MB-231 cells. The mature form of MMP-9 (92 kDa, upper band) possessed gelatinolytic activity and was detected outside the cells, while the precursor form (85 kDa, lower band) remained inside the cells; these findings were consistent with the results of previous studies (24,25). Transcriptional regulation of MMP-9 has been proposed to be vital in its activation (26).…”

Change in Adiponectin and Oxidative Stress after Modifiable Lifestyle Interventions in Breast Cancer Cases

“…Also, Habib et al (2008) reported that ginger might act as an anti-inflammatory and anti-cancer (Habib et al, 2008). The dried rhizomes of ginger (rich in pungent phenolic compounds: gingerols and shogaols) or extracts thereof are important ingredients of many traditional/ alternative medicines worldwide (Ling et al, 2010). Both of 6-shogaol and 6-gingerol can significantly inhibit the down-regulation of adiponectin expression (Yasuka et al, 2008).…”

“…In Asian countries, ginger has also been used as an herbal medicine to treat a wide range of disorders such as inflammation, dyspepsia, nausea, vomiting, pain, the common cold and diarrhoea (Ling et al, 2010). Ginger extract has antioxidant properties and scavenges superoxide anion and hydroxyl radicals (Afshari et al, 2007).…”

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

“…[6]-Shogaol, one of the active ingredients in ginger, was identified to possess a surprisingly wide range of beneficial properties. It has been reported that [6]-shogaol can inhibit breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via the blockade of nuclear factor-kappaB activation [24] .…”

“…[6]-Shogaol, an active ingredient in ginger, was previously reported to possess anti-cancer and anti-inflammatory properties [23,24] . However, despite many published reports, the effect of [6]-shogaol on melanogenesis is unknown.…”