https://scholars.lib.ntu.edu.tw/handle/123456789/292366
標題: | Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells | 作者: | Pan, M.-H. Chang, W.-L. Lin-Shiau, S.-Y. Ho, C.-T. Lin, J.-K. MIN-HSIUNG PAN |
關鍵字: | Apoptosis; Caspase-2; Caspase-3; Caspase-9; Caspase-activated deoxyribonuclease; Curcumin; Cytochrome c; DNA fragmentation factor; Garcinol; Poly-(ADP-ribose) polymerase | 公開日期: | 2001 | 卷: | 49 | 期: | 3 | 起(迄)頁: | 1464-1474 | 來源出版物: | Journal of Agricultural and Food Chemistry | 摘要: | Garcinol, a polyisoprenylated benzophenone, was purified from Garcinia indica fruit rind. The effects of garcinol and curcumin on cell viability in human leukemia HL-60 cells were investigated. Garcinol and curcumin displayed strong growth inhibitory effects against human leukemia HL-60 cells, with estimated IC50 values of 9.42 and 19.5 μM, respectively. Garcinol was able to induce apoptosis in a concentration- and time-dependent manner; however, curcumin was less effective. Treatment with garcinol caused induction of caspase-3/CPP32 activity in a dose- and time-dependent manner, but not caspase-1 activity, and induced the degradation of poly(ADP-ribose) polymerase (PARP). Pretreatment with caspase-3 inhibitor inhibited garcinol-induced DNA fragmentation. Treatment with garcinol (20 μM) caused a rapid loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. The cleavage of D4-GDI, an abundant hematopoietic cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, occurred simultaneously with the activation of caspase-3 but preceded DNA fragmentation and the morphological changes associated with apoptotic cell death. Of these, Bcl-2, Bad, and Bax were studied. The level of expression of Bcl-2 slightly decreased, while the levels of Bad and Bax were dramatically increased in cells treated with garcinol. These results indicate that garcinol allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces DFF-45 (DNA fragmentation factor) degradation. It is suggested that garcinol-induced apoptosis is triggered by the release of cytochrome c into the cytosol, procaspase-9 processing, activation of caspase-3 and caspase-2, degradation of PARP, and DNA fragmentation caused by the caspase-activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by garcinol may provide a pivotal mechanism for its cancer chemopreventive action. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-0034836540&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/292366 |
DOI: | 10.1021/jf001129v | SDG/關鍵字: | benzophenone; caspase; caspase 3; curcumin; cytochrome c; DNA fragment; garcinol; interleukin 1beta converting enzyme; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein BAD; protein Bax; protein bcl 2; unclassified drug; apoptosis; article; cell viability; enzyme activation; enzyme activity; enzyme degradation; enzyme release; human; human cell; leukemia cell; membrane potential; protein expression; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Survival; Curcumin; Cysteine Proteinase Inhibitors; Cytochrome c Group; Enzyme Activation; HL-60 Cells; Humans; Intracellular Membranes; Membrane Potentials; Mitochondria; Oligopeptides; Terpenes; Garcinia indica |
顯示於: | 食品科技研究所 |
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