| Summary: | 碩士 === 中山醫學大學 === 營養學研究所 === 97 === Several sulfur compounds are recognized as potential chemopreventive compounds. This protection is related to the induction of phase II detoxification enzymes. We previously reported that diallyl disulfide (DADS) and diallyl trisulfide (DATS) up-regulate the gene expression of the pi class of glutathione
S-transferase (GSTP) in Clone 9 liver cells, but whether the other sulfur compounds have the same ability are unknown. In the present study, we explore the modulatory of three sulfur compounds including α-lipoic acid (LA), dihydrolipoic acid (DHLA) and sulforaphane (SFN) on the gene expression of GSTP. As results indicated, LA (50, 200 and 600 μM), DHLA (50, 200 and 600 μM), and SFN (0.2, 1 and 5 μM) increased GSTP protein expression, mRNA and enzyme activity in a concentration-dependently manner. Then we further investigated the signal pathway. In the presence DADS (50 μM), DATS (50 μM), LA (600 μM), DHLA (600 μM), and SFN (5 μM) increase extracellular signal-regulated kinase (ERK) and phosphatidylinosotol 3-kinase/Akt phosphorylation in 5 min, but not c-Jun NH2-terminal kinase (JNK) and p38. Pretreatment of cells with PD98059 (ERK inhibitor) or wortmannin (PI3K inhibitor) suppressed the induction of ERK and Akt activation by sulfur compounds, respectively. And we finally determined whether the up-regulation of GSTP protein expression by sulfur compounds was mainly inhibited by PD98059, not by wortmannin. Electromobility gel shift assay (EMSA) showed that upon treatment with LA, DHLA, and SFN, the DNA binding activity of AP-1, were started to induce at 15 min. After pretreatment with the PD98059, however, the increase in AP-1 binding to DNA were abolished. In conclusion, the effectiveness of three sulfur compounds: LA, DHLA, and SFN is likely related to the ERK/AP-1 signaling pathway in Clone 9 liver cells.
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