請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/62081
標題: Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells
作者: Yeh, C.T.
顏國欽
Yen, G.C.
關鍵字: antioxidant response element
drug-metabolizing-enzymes
gene-expression
chemopreventive agent
transcription factor
mediated
apoptosis
cycle arrest
cancer cells
isothiocyanate sulforaphane
phenethyl isothiocyanate
期刊/報告no:: Carcinogenesis, Volume 26, Issue 12, Page(s) 2138-2148.
摘要: The molecular mechanism of sulforaphane on the induction of metallothionein (MT) genes in HepG2 cells and the antiproliferative effects of sulforaphane were investigated in this study. Treatment of the cells with sulforaphane at non-toxicity concentration (0-20 mu M) resulted in coordinate increases in the induction of MT-I and MT-II mRNA, followed by corresponding increases in MT protein expression. Western blot analysis revealed the increased level of the transcription factor, Nrf2 in a time-dependent manner from sulforaphane-treated cells. Furthermore, sulforaphane activated the extracellular signal-regulated protein kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways. SB203580, a specific inhibitor of p38 and PD98059, a specific inhibitor of ERK, abolished sulforaphane-induced MT protein expression, whereas SP600125, a specific inhibitor of JNK, had no significant effect. At relatively high concentration (30-100 mu M), sulforaphane is a cell growth modulator, as it induced apoptotic cell death characterized by internucleosomal DNA fragmentation and caused a rapid induction of caspase 3 activity, according to the appearance of the caspase 3 fragments and stimulated proteolytic cleavage of poly (ADP-ribose) polymerase in a time-dependent manner. Moreover, sulforaphane-induced apoptotic cell death was accompanied by upregulation of Bax and downregulation of Bcl-2 and Bcl-X-l protein. Sulforaphane-induced DNA fragmentation was blocked by the N-acetyl-l-cysteine and catalase, suggesting that the death signaling was triggered by oxidative stress. Taken together these results strongly suggest that at low concentrations of sulforaphane, activation of MAPKs, such as ERK and p38 pathway, lead to Nrf2-mediated MT gene expression. Whereas at a higher concentration, sulforaphane is an effective apoptosis inducer in HepG(2) cells through regulation of Bcl-2 family molecular and activation of ICE/Ced-3 protease (caspase 3) cascade. The results from this study may provide more evidence for its chemopreventive function.
URI: http://hdl.handle.net/11455/62081
ISSN: 0143-3334
文章連結: http://dx.doi.org/10.1093/carcin/bgi185
顯示於類別:食品暨應用生物科技學系

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