6‐Shogaol is more effective than 6‐gingerol and curcumin in inhibiting 12‐O‐tetradecanoylphorbol 13‐acetate‐induced tumor promotion in mice

Abstract

We previously reported that 6-shogaol strongly suppressed lipopolysaccharide-induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrate that topical application of 6-shogaol more effectively inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB subunits. 6-Shogaol also reduced TPA-induced phosphorylation of IkappaBalpha and p65, and caused subsequent degradation of IkappaBalpha. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulate kinase1/2, p38 mitogen-activated protein kinase, JNK1/2, and phosphatidylinositol 3-kinase/Akt, which are upstream of nuclear factor-kappaB and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 wk. Presented data reveal for the first time that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that 6-shogaol is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

Metabolism of [6]-Shogaol in Mice and in Cancer Cells

“…Kim et al (2008) (Sang et al, 2009). Along with our collaborators, we have reported that [6]-shogaol was more effective than [6]-gingerol in inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mice (Wu et al, 2010). Furthermore, Dugasani et al (2010) The pharmacokinetics of [6]-shogaol in mice and in humans have been investigated (Zick et al, 2008(Zick et al, , 2010Wang et al, 2009;Asami et al, 2010;Iwabu et al, 2010).…”

“…It has been reported that shogaols are minor components in fresh ginger, and the ratio of [6]-shogaol to [6]-gingerol is approximately 1:1 in dried ginger (Govindarajan, 1982a,b;Sang et al, 2009;Wu et al, 2010).…”

Examination of the Pharmacokinetics of Active Ingredients of Ginger in Humans

“…Gingerols (especially 6-gingerol) are the major components in the fresh ginger rhizome. The amount of shogaols is increased in the dried ginger, as evidenced by the reduction of the ratio of 6-gingerol to 6-shogaol from 10:1 in fresh ginger to 1:1 in dried ginger (17,18,20).…”

Effects of Pretreatments and Drying Temperatures on Drying Characteristics, Antioxidant Properties and Color of Ginger Slice

“…It has been used for the treatment of migraine headaches, muscular aches, pains, sore throats, common cold, fl u-like symptoms, indigestion and even painful menstrual periods (Dugasani et al, 2010;El-Ghorab et al, 2010). Moreover, ginger contains phenolic compounds such as gingerols, zingerone and shogaols, which possess antioxidant, anti-infl ammatory and anticancer properties (Stoilova et al, 2007;Chen et al, 2008;Dugasani et al, 2010;Wu et al, 2010). Kaur and Kapoor (2002) determined the total phenolic content (TPC) of 36 vegetables in Asia including ginger.…”

“…It has been reported that TPC and antioxidant activity of ginger increased a er drying (Puengphian and Sirichote, 2008). This is due to the conversion of 6-gingerol, which is the most abundant component in the fresh ginger rhizome, to 6-shogaol during drying (Balladin et al, 1996;Ali et al, 2008;Wu et al, 2010). Dugasani et al (2010) reported that 6-shogaol has exhibited more potent antioxidant properties than gingerols; the scavenging potential was in the order of 6-shogaol > 10-gingerol > 8-gingerol > 6-gingerol.…”