| Summary: | 碩士 === 國立高雄海洋科技大學 === 水產食品科學研究所 === 95 === PART I:Ginger, the rhizome of Zingiber officinale, known commonly as ginger, is consumed worldwide as a spice and a flavoring agent. It has been used in traditional medicine with carminative effect, anti-nausea, anti-inflammatory, and anti-carcinogenic properties. This study examined the growth inhibitory effects of the structurally related gingerols and shogaols compounds in human cancer cells. The effects of 6-shogaol on cell viability in human colorectal carcinoma COLO 205 cells were investigated. This study demonstrated that 6-shogaol was able to inhibit cell proliferation and induce apoptosis in a concentration- and time-dependent manner. 6-Shogaol-induced cell death was characterized with changes in nuclear morphology, DNA fragmentation, and cell morphology. The molecular mechanism of 6-shogaol-induced apoptosis was also investigated. Treatment with 6-shogaol caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly (ADP-riobse) polymerase. Furthermore, treatment with 6-shogaol caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS), release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The stress-inducible transcription factor known as growth and DNA damage (GADD)-inducible transcription factor 153 (GADD 153) mRNA and protein is markedly induced in a time- and concentration- dependent manner in response to 6-shogaol. NAC prevented up-regulation of GADD153 mRNA and protein expression caused by 6-shogaol. These findings for the first time suggest that 6-shogaol creates an oxidative cellular environment that induces DNA damage and GADD153 gene activation, which in turn helps trigger apoptosis in COLO 205 cells. The induction of apoptosis by 6-shogaol may provide a pivotal mechanism for its cancer chemopreventive action.
PART II:Ginger rhizome (Zingiber officinale Roscoe, Zingiberaceae), known commonly as ginger, is consumed worldwide as a spice and a flavoring agent. In particular, it has been used in traditional oriental medicine against symptoms such as common cold, inflammation, rheumatic disorders and gastrointestinal discomforts. The purpose of this study was to clarify the molecule mechanism of 6-shogaol on anti-inflammation and anti-tumor promoting activities in vitro and in vivo. We have demonstrated that 6-shogaol strongly suppressed the lipopolysaccharide (LPS)-induced NO and PGE2 production in RAW264.7 macrophage. Incubation of RAW264.7 macrophage with 6-shogaol decreased LPS-induced iNOS and COX-2 protein and mRNA expression. In additional, 6-shogaol inhibited LPS-induced phosphorylation as well as degradation of IB. 6-Shogaol also inhibited LPS-induced activation of ERK and PI3K/ AKT, but not p38 MAPK. Further investigations showed that the topical application of 6-shogaol before 12-O-tetradecanoylphorbol-13-acetate (TPA) treated significantly inhibits TPA-induced mouse skin inflammation and TPA-induced tumor promotion in mouse skin. The pretreatment with 6-shogaol inhibited the expression of iNOS and COX-2 proteins and NF-B activation in mouse skin with TPA-induced acute inflammation. In addition, 6-shogaol significantly inhibited 7, 12-dimethylbenz[a]anthracene (DMBA)/ TPA-induced skin tumor formation by reducing the number and size of tumors while it did not influence the tumor incidence. Taken together, the present study demonstrates that 6-shogaol may exert its anti-inflammation and anti-tumor promoting activities which provide a pivotal mechanism for cancer chemopreventive action.
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