| Summary: | 碩士 === 國立高雄海洋科技大學 === 水產食品科學研究所 === 97 === Part I Garcinol inhibits cell growth and induces apoptosis in human Hep3B cells
Garcinol (camboginol), a polyisoprenylated benzophenone derivative, is present in Guttiferae (Garcinia indica, Garcinia cambogia and Garcinia huillkensis). Garcinia (cv. Kokum) is used as a garnish for curry and in some of the folk medicine in India, and is a rich source of secondary metabolites including xanthones, flavanoids, benzophenones, lactones and phenolic acids. This study demonstrated that garcinol was able to inhibit cell proliferation and induce apoptosis in a dose- and time-dependent manner. Garcinol induced cell death was characterized with changes in nuclear morphology, DNA fragmentation, and cell morphology. Treatment with 50 M garcinol caused induction of caspase-3, -8 and -9 activity in a time-dependent manner, but not caspase-1 activity and induced the degradation of PARP and DFF-45. Furthermore, treatment with garcinol (50 M) 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. In Bcl-2 family protein, treatment with garcinol (50 M) caused accure protein of performance the Bax. The stress-inducible transcription factor known as growth and DNA damage (GDAA) -inducible transcription factor 153 (GADD153) protein is markedly induced in a dose- and time- dependent manner in response to garcinol. Based on the above results, garcinol can be effectively induced apoptosis in human Hep3B hepatoma cells with anti-liver cancer activity, and hopes to further animal experiments to explore its effectiveness, the future can provide as a people in prevention and treatment of liver cancer of the new reagent.
Part II Garcinol inhibits TPA-induced acute inflammation and DMBA-TPA two-stage mouse skin carcinogenesis
Further investigations showed that the topical application of garcinol 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 garcinol inhibited the expression of iNOS, COX-2 and ODC proteins with of iNOS and COX-2 mRNA in mouse skin with TPA-induced acute inflammation.In addition, garcinol significantly reduced the phosphorylation and degradation of IB by TPA which may through down-regulation of IB kinase (IKK) activity and following avtivation of NF-B. Garcinol also inhibited TPA-induced Mitogen-activated kinases (MAPKs) and Phosphatidylinositol 3-kinase (PI3K)/Akt activation. In addition, garcinol significantly inhibited 7, 12-dimethylbenz [] anthracene (DMBA)/TPA-induced skin tumor formation by reducing the number, size and weight of tumors, and lower the tumors incidence effectively. Taken together, the present study demonstrates the garcinol may exert its anti-inflammation and anti-tumor promoting activities which provide a pivotal mechanism for cancer chemopreventive action.
|
|---|
