6‐Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression

Abstract

Ginger, the rhizome of Zingiber officinale, is a traditional medicine with anti-inflammatory and anticarcinogenic properties. This study examined the growth inhibitory effects of the structurally related compounds 6-gingerol and 6-shogaol on human cancer cells. 6-Shogaol [1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one] inhibits the growth of human cancer cells and induces apoptosis in COLO 205 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in the early stages of 6-shogaol-induced apoptosis, preceding cytochrome c release, caspase activation, and DNA fragmentation. Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.

6-Shogaol from Dried Ginger Inhibits Growth of Prostate Cancer Cells Both In Vitro and In Vivo through Inhibition of STAT3 and NF-κB Signaling

“…Previously published studies have shown the potential antiproliferative and apoptosis inducing activity of 6-SHO in lung, colorectal, liver and, hematologic cancer cells (15,(30)(31)(32). In the present study, 6-SHO was also shown to be effective at inhibiting the growth of HMVP2 cells in vivo.…”

“…Given that 6-SHO effectively inhibited the growth of prostate cancer cells regardless of STAT3 expression or activity, multiple mechanisms are likely involved in its effects on prostate cancer cell survival, including effects on STAT3, NF-kB, and possibly other signaling pathways. In this regard, it has been reported that 6-SHO induces apoptosis by generation of reactive oxygen species in human colorectal cancer cells, by directly regulating Akt1/2 in nonsmall cell lung carcinoma cells and by modulation of estrogen receptor stress in hepatocellular carcinoma cells (23,32,43). In addition, as shown in Fig.…”

Preventive and Curative Effects of Zingiber officinale Extract against Histopathological and Ki-67 Immunohistochemical Changes of Glycerol-Induced Acute Renal Failure in Rat

“…The results of this study indicate that extract of ginger alone rendered significant protection against glycerol-induced nephrotoxicity which was evident from the lowered serum urea and creatinine levels. These findings are consistent with previous studies that suggested that the chemopreventive properties of ginger may lie in its ability to regulate viability and cell function (Pan et al, 2008).…”

Role of 6-Shogaol in <b><i>Tert</i></b>-Butyl Hydroperoxide-Induced Apoptosis of HepG2 Cells

“…Antioxidative effects of 6-shogaol are consistent with the recent results, which showed that 6-shogaol-rich ginger extract could enhance antioxidant defense systems in cells and mice [18]. Several reports indicated that 6-shogaol could induce apoptosis at high concentrations [30,31]. In human colorectal carcinoma cells, apoptotic cell death was induced by 60 μmol/l of 6-shogaol via ROS generation, MMP modulation and caspase activation [30].…”