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研究生:鄭伊評
研究生(外文):Yi-Ping
論文名稱:探討飲食中不同含硫化合物對大鼠肝細胞pi屬麩胱甘肽硫轉移酶表現及其分子機制
論文名稱(外文):Effect and mechanism of dietary sulfur compounds up-regulate the gene expression of the pi class of glutathione S-transferase in rat liver Clone 9 cells.
指導教授:劉承慈李宗貴
指導教授(外文):Cheng-Tzu LiuChong-Kuei Lii
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:營養學研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:80
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許多研究皆指出含硫化合物對人類疾病有不等程度的預防作用,並具有抗腫瘤與誘發phase II生物轉換酵素的特性。過去本實驗室已發現存於蔥蒜中的有機硫化物 (organosulfur compounds, OSCs)包括diallyl disulfide (DADS)和diallyl trisulfide (DATS)可以上調大鼠Clone 9細胞pi屬麩胱甘肽硫轉移酶 (glutathione S-transferase, GSTP)基因的表現,然而其他非屬大蒜的含硫化合物是否也有相同的調控機轉則是未知的,因此本實驗即要比較其他非屬大蒜的含硫化合物硫辛酸 (α-lipoic acid, LA)、還原型硫辛酸 (dihydrolipoic acid, DHLA)和蘿蔔硫素 (sulforaphane, SFN)對於調控GSTP表現的作用機轉。本實驗以大鼠Clone 9肝細胞株為實驗模式,結果顯示,將Clone 9細胞分別培養於不同濃度LA (50、200和600 μM)、DHLA (50、200和600 μM)、SFN (0.2、1和5 μM)之培養基,皆以劑量關係誘發GSTP的蛋白質、mRNA和酵素活性表現。接著我們繼續研究LA 、DHLA和SFN調控 GSTP的分子機轉。以Western blot分析,若處理DADS (50 μM)、DATS (50 μM)、LA (600 μM)、DHLA (600 μM)和SFN(5 μM)皆可促進extracellular signal-regulated kinase (ERK)和phosphatidylinositol 3-kinase (PI3K) /Akt的磷酸化作用,但不影響 c-Jun NH2-terminal kinase (JNK)和p38蛋白質。預處理20 μM PD98059 (ERK抑制劑)亦能抑制DADS、DATS、LA、DHLA和SFN的p-ERK和GSTP的蛋白質表現,但預處理1 μM wortmannin (PI3K抑制劑)後雖然可以抑制p-Akt但GSTP並無受到抑制。另外由Electromobility gel shift assay (EMSA)結果顯示,細胞處理LA (600 μM)、DHLA (600 μM)和SFN (5 μM)會增加AP-1活化,而使用PD98059則會破壞此AP-1的結合作用。結論:不同含硫化合物DADS、DATS、LA、DHLA、和SFN上調GSTP基因表現與ERK/AP-1訊號途徑有關。

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.


目錄
目錄.............................Ⅰ
圖次.............................III
表次............................. V
縮寫表............................VI
中文摘要 ...........................1
英文摘要 ...........................2
第一章 文獻回顧
(一) 飲食中含硫化合物與疾病的關係
1-1自由基、活性氧對生物體的傷害............4
1-2 硫的特性及生理功能.................5
1-3 大蒜有機含硫化合物 (organosulfur compounds, OSCs)...5
1-4 α-硫辛酸 (α-lipoic acid; LA)和二氫硫辛酸 (dihydrolipoic acid; DHLA) ....................7
1-5 蘿蔔硫素 (sulforaphane, SFN) ............10
(二) 生物體之抗氧化防禦系統
2-1麩胱甘肽 (glutathione, GSH) .............12
2-2生物轉換酵素系統 (biotransformation enzyme system) ..14
2-2.1 NAD(P)H : quinone oxidoreductase 1 (NQO1)....16
2-2.2麩胱甘肽硫轉移酶 (glutathione S-transferase, GSTs).16
2-2.3 GSTP ....................17
2-2.4 Activator protein-1 (AP-1)............18
2-2.5 Mitogen-activated protein kinases (MAPK) .....18
2-2.6 PI3K (phosphatidylinositol 3-kinase)/Aktpathway .. 19
第二章 實驗動機與目的 ....................22
第三章 實驗材料與方法 ....................23
(一) 研究架構........................23
(二) 實驗細胞株.......................24
(三) 化學試劑........................24
(四) 實驗方法........................28
4-1大鼠Clone 9細胞的培養與處理..... ......28
4-2細胞存活率分析 (MTT assay) ............29
4-3蛋白質表現量分析.................30
4-4酵素活性分析...................32
4-5 Reverse Transcription-Polymerase Chain Reaction
(real time-PCR)...................33
4-6 Electrophoretic mobility shift assay (EMSA) .......35
(五) 統計方法 .......................36
第四章 實驗結果與圖表 .....................37
第五章 討論..........................57
第六章 結論..........................63
第七章 附錄..........................64
第八章 參考文獻........................69









圖次
文獻回顧
圖一、DADS和DATS的化學結構 ................6
圖二、LA和DHLA的化學結構..................8
圖三、LA和DHLA參與抗氧化劑的再生..............9
圖四、硫代配醣體 (glucosinolate)的生物轉化 (bioconversion)路徑.....10
圖五、SFN的化學結構.....................12
圖六、PI3K/Akt 的訊號途徑...................20
結果
圖一、不同含硫化合物 (LA、DHLA和SFN)對Clone 9細胞存活率之影
響...........................42
圖二、不同含硫化合物對Clone 9細胞GSTP蛋白質表現之影響 ...43
圖三、不同含硫化合物對Clone 9細胞GSTP mRNA表現之影響 ...44
圖四、不同含硫化合物對Clone 9細胞GSTP酵素活性之影響 ....45
圖五、不同含硫化合物對Clone 9細胞ERK1/2蛋白質磷酸化之影響..46
圖六、不同含硫化合物對Clone 9細胞JNK蛋白質磷酸化之影響...47
圖七、不同含硫化合物對Clone 9細胞p38蛋白質磷酸化之影響 ...48
圖八、不同含硫化合物對Clone 9細胞Akt蛋白質磷酸化之影響 ...49
圖九、ERK抑制劑PD98059對不同含硫化合物誘發Clone 9細胞ERK1/2
蛋白質磷酸化之影響 ................... 50
圖十、PI3K抑制劑wortmannin對不同含硫化合物誘發Clone 9細胞Akt
蛋白質磷酸化之影響 ................... 51
圖十一、PI3K抑制劑LY294002對不同含硫化合物誘發Clone 9細胞Akt
蛋白質磷酸化之影響.................. 52
圖十二、ERK抑制劑PD98059對不同含硫化合物誘發Clone 9細胞GSTP
蛋白質表現之影響 ................... 53
圖十三、 PI3K抑制劑wortmannin對不同含硫化合物誘發Clone 9細胞GSTP蛋白質表現之影響 ................54
圖十四、PI3K抑制劑LY294002對不同含硫化合物誘發Clone 9細胞GSTP 蛋白質表現之影響................... 55
圖十五、不同含硫化合物對Clone 9細胞內AP-1之DNA binding site活性之影響........................ 56
附錄
圖一、不同含硫化合物對Clone 9細胞GST酵素活性之影響..... 64
圖二、不同含硫化合物對Clone 9細胞NQO1蛋白質表現之影響 ...65
圖三、不同含硫化合物對Clone 9細胞HO-1蛋白質表現之影響....66
圖四、不同含硫化合物對Clone 9細胞ERK1/2蛋白質磷酸化之影響..67













表次
表一、AP-1 DNA binding site序列................. 68
表二、1°Ab或2°Ab稀釋比例.................. 68


行政院衛生署:97年度死因統計 (2008)
Aggarwal, B. B. and Shishodia, S. (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 71, 1397-421.
Angel, P., Imagawa, M., Chiu, R., Stein, B., Imbra, R. J., Rahmsdorf, H. J., Jonat, C., Herrlich, P. and Karin, M. (1987) Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 49, 729-39.
Angel, P. and Karin, M. (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1072, 129-57.
Ariga, T., Oshiba, S. and Tamada, T. (1981) Platelet aggregation inhibitor in garlic. Lancet. 1, 150-1.
Asada, K., Asada, R., Yoshiji, H., Fukui, H., Floyd, R. A. and Kotake, Y. (2006) DNA cytosine methylation profile in various cancer-related genes is altered in cultured rat hepatocyte cell lines as compared with primary hepatocytes. Oncol Rep. 15, 1241-8.
Bacon, J. R., Williamson, G., Garner, R. C., Lappin, G., Langouet, S. and Bao, Y. (2003) Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes. Carcinogenesis. 24, 1903-11.
Barcelo, S., Mace, K., Pfeifer, A. M. and Chipman, J. K. (1998) Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5-f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane. Mutat Res. 402, 111-20.
Battin, E. E. and Brumaghim, J. L. (2009) Antioxidant Activity of Sulfur and Selenium: A Review of Reactive Oxygen Species Scavenging, Glutathione Peroxidase, and Metal-Binding Antioxidant Mechanisms. Cell Biochem Biophys.
Beckett, G. J. and Hayes, J. D. (1993) Glutathione S-transferases: biomedical applications. Adv Clin Chem. 30, 281-380.
Begleiter, A., Sivananthan, K., Lefas, G. M., Maksymiuk, A. W. and Bird, R. P. (2009) Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats. Oncol Rep. 21, 1559-65.
Berhane, K., Widersten, M., Engstrom, A., Kozarich, J. W. and Mannervik, B. (1994) Detoxication of base propenals and other alpha, beta-unsaturated aldehyde products of radical reactions and lipid peroxidation by human glutathione transferases. Proc Natl Acad Sci U S A. 91, 1480-4.
Biewenga, G. P., Haenen, G. R. and Bast, A. (1997) The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 29, 315-31.
Bilska, A., Dubiel, M., Sokolowska-Jezewicz, M., Lorenc-Koci, E. and Wlodek, L. (2007) Alpha-lipoic acid differently affects the reserpine-induced oxidative stress in the striatum and prefrontal cortex of rat brain. Neuroscience. 146, 1758-71.
Bilska, A. and Wlodek, L. (2005) Lipoic acid - the drug of the future? Pharmacol Rep. 57, 570-7.
Block, G., Patterson, B. and Subar, A. (1992) Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer. 18, 1-29.
Brunet, A., Datta, S. R. and Greenberg, M. E. (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol. 11, 297-305.
Bueno de Mesquita, H. B., Maisonneuve, P., Runia, S. and Moerman, C. J. (1991) Intake of foods and nutrients and cancer of the exocrine pancreas: a population-based case-control study in The Netherlands. Int J Cancer. 48, 540-9.
Chang, K. T., Lii, C. K., Tsai, C. W., Yang, A. J. and Chen, H. W. (2008) Modulation of the expression of the pi class of glutathione S-transferase by Andrographis paniculata extracts and andrographolide. Food Chem Toxicol. 46, 1079-88.
Cheng, J. Q., Lindsley, C. W., Cheng, G. Z., Yang, H. and Nicosia, S. V. (2005) The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene. 24, 7482-92.
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., 3rd, Kaestner, K. H., Bartolomei, M. S., Shulman, G. I. and Birnbaum, M. J. (2001) Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science. 292, 1728-31.
Dengel, D. R., Hagberg, J. M., Pratley, R. E., Rogus, E. M. and Goldberg, A. P. (1998) Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men. Metabolism. 47, 1075-82.
Derijard, B., Raingeaud, J., Barrett, T., Wu, I. H., Han, J., Ulevitch, R. J. and Davis, R. J. (1995) Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science. 267, 682-5.
Dhakshinamoorthy, S. and Jaiswal, A. K. (2001) Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene. Oncogene. 20, 3906-17.
Druesne, N., Pagniez, A., Mayeur, C., Thomas, M., Cherbuy, C., Duee, P. H., Martel, P. and Chaumontet, C. (2004) Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis. 25, 1227-36.
Duenschede, F., Erbes, K., Riegler, N., Ewald, P., Kircher, A., Westermann, S., Schad, A., Miesmer, I., Albrecht-Schock, S., Gockel, I., et al. (2007) Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model. World J Gastroenterol. 13, 3692-8.
Elangovan, S. and Hsieh, T. C. (2008) Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. Int J Oncol. 33, 833-8.
Evans, W. J. (1999) Exercise training guidelines for the elderly. Med Sci Sports Exerc. 31, 12-7.
Fahey, J. W. and Talalay, P. (1999) Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol. 37, 973-9.
Fimognari, C. and Hrelia, P. (2007) Sulforaphane as a promising molecule for fighting cancer. Mutat Res. 635, 90-104.
Flagg, E. W., Coates, R. J., Eley, J. W., Jones, D. P., Gunter, E. W., Byers, T. E., Block, G. S. and Greenberg, R. S. (1994) Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level. Nutr Cancer. 21, 33-46.
Fleischauer, A. T. and Arab, L. (2001) Garlic and cancer: a critical review of the epidemiologic literature. J Nutr. 131, 1032S-40S.
Flier, J., Van Muiswinkel, F. L., Jongenelen, C. A. and Drukarch, B. (2002) The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. Free Radic Res. 36, 695-9.
Force, T. and Bonventre, J. V. (1998) Growth factors and mitogen-activated protein kinases. Hypertension. 31, 152-61.
Foster, T. S. (2007) Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy. Diabetes Educ. 33, 111-7.
Fukao, T., Hosono, T., Misawa, S., Seki, T. and Ariga, T. (2004) The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride. Food Chem Toxicol. 42, 743-9.
Gao, A., Liu, B., Shi, X., Jia, X., Ye, M., Jiao, S., You, B. and Huang, C. (2007) Phosphatidylinositol-3 kinase/Akt/p70S6K/AP-1 signaling pathway mediated benzo(a)pyrene-induced cell cycle alternation via cell cycle regulatory proteins in human embryo lung fibroblasts. Toxicol Lett. 170, 30-41.
Getahun, S. M. and Chung, F. L. (1999) Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress. Cancer Epidemiol Biomarkers Prev. 8, 447-51.
Gopalakrishnan, A. and Tony Kong, A. N. (2008) Anticarcinogenesis by dietary phytochemicals: cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-kappa B and AP-1 in abnormal cancer cells. Food Chem Toxicol. 46, 1257-70.
Guyton, K. Z., Liu, Y., Gorospe, M., Xu, Q. and Holbrook, N. J. (1996) Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem. 271, 4138-42.
Halliwell, B. (1994) Free radicals and antioxidants: a personal view. Nutr Rev. 52, 253-65.
Hamada, S., Kamada, M., Furumoto, H., Hirao, T. and Aono, T. (1994) Expression of glutathione S-transferase-pi in human ovarian cancer as an indicator of resistance to chemotherapy. Gynecol Oncol. 52, 313-9.
Han, S. S., Keum, Y. S., Seo, H. J., Chun, K. S., Lee, S. S. and Surh, Y. J. (2001) Capsaicin suppresses phorbol ester-induced activation of NF-kappaB/Rel and AP-1 transcription factors in mouse epidermis. Cancer Lett. 164, 119-26.
Handelman, G. J., Han, D., Tritschler, H. and Packer, L. (1994) Alpha-lipoic acid reduction by mammalian cells to the dithiol form, and release into the culture medium. Biochem Pharmacol. 47, 1725-30.
Hanlon, N., Okpara, A., Coldham, N., Sauer, M. J. and Ioannides, C. (2008) Modulation of rat hepatic and pulmonary cytochromes P450 and phase II enzyme systems by erucin, an isothiocyanate structurally related to sulforaphane. J Agric Food Chem. 56, 7866-71.
Hara, M., Hanaoka, T., Kobayashi, M., Otani, T., Adachi, H. Y., Montani, A., Natsukawa, S., Shaura, K., Koizumi, Y., Kasuga, Y., et al. (2003) Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a multicenter, hospital-based case-control study in Japan. Nutr Cancer. 46, 138-47.
Harter, J. M. and Baker, D. H. (1977) Sulfur amino acid activity of glutathione, DL-alpha-hydroxy-methionine, and alpha-keto-methionine in chicks. Proc Soc Exp Biol Med. 156, 201-4.
Hayes, J. D., Flanagan, J. U. and Jowsey, I. R. (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol. 45, 51-88.
He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. and Alam, J. (2001) Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem. 276, 20858-65.
Henderson, C. J., Smith, A. G., Ure, J., Brown, K., Bacon, E. J. and Wolf, C. R. (1998) Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases. Proc Natl Acad Sci U S A. 95, 5275-80.
Herrera, B., Carracedo, A., Diez-Zaera, M., Guzman, M. and Velasco, G. (2005) p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells. FEBS Lett. 579, 5084-8.
Himes, S. R., Sester, D. P., Ravasi, T., Cronau, S. L., Sasmono, T. and Hume, D. A. (2006) The JNK are important for development and survival of macrophages. J Immunol. 176, 2219-28.
Hu, R., Xu, C., Shen, G., Jain, M. R., Khor, T. O., Gopalkrishnan, A., Lin, W., Reddy, B., Chan, J. Y. and Kong, A. N. (2006) Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice. Cancer Lett. 243, 170-92.
Hu, X., Benson, P. J., Srivastava, S. K., Mack, L. M., Xia, H., Gupta, V., Zaren, H. A. and Singh, S. V. (1996) Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic. Arch Biochem Biophys. 336, 199-214.
Hughes, V. A., Fiatarone, M. A., Fielding, R. A., Ferrara, C. M., Elahi, D. and Evans, W. J. (1995) Long-term effects of a high-carbohydrate diet and exercise on insulin action in older subjects with impaired glucose tolerance. Am J Clin Nutr. 62, 426-33.
Ikeda, H., Nishi, S. and Sakai, M. (2004) Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis. Biochem J. 380, 515-21.
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D. and Yamamoto, M. (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13, 76-86.
Itoh, N., Semba, S., Ito, M., Takeda, H., Kawata, S. and Yamakawa, M. (2002) Phosphorylation of Akt/PKB is required for suppression of cancer cell apoptosis and tumor progression in human colorectal carcinoma. Cancer. 94, 3127-34.
Jakubikova, J., Sedlak, J., Mithen, R. and Bao, Y. (2005) Role of PI3K/Akt and MEK/ERK signaling pathways in sulforaphane- and erucin-induced phase II enzymes and MRP2 transcription, G2/M arrest and cell death in Caco-2 cells. Biochem Pharmacol. 69, 1543-52.
James, S. R., Downes, C. P., Gigg, R., Grove, S. J., Holmes, A. B. and Alessi, D. R. (1996) Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem J. 315 ( Pt 3), 709-13.
Joseph, M. A., Moysich, K. B., Freudenheim, J. L., Shields, P. G., Bowman, E. D., Zhang, Y., Marshall, J. R. and Ambrosone, C. B. (2004) Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer. 50, 206-13.
Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J. and Waterfield, M. D. (2001) Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 17, 615-75.
Kensler, T. W. (1997) Chemoprevention by inducers of carcinogen detoxication enzymes. Environ Health Perspect. 105 Suppl 4, 965-70.
Keum, Y. S., Jeong, W. S. and Kong, A. N. (2004) Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms. Mutat Res. 555, 191-202.
Kirby, G. M., Wolf, C. R., Neal, G. E., Judah, D. J., Henderson, C. J., Srivatanakul, P. and Wild, C. P. (1993) In vitro metabolism of aflatoxin B1 by normal and tumorous liver tissue from Thailand. Carcinogenesis. 14, 2613-20.
Komarnisky, L. A., Christopherson, R. J. and Basu, T. K. (2003) Sulfur: its clinical and toxicologic aspects. Nutrition. 19, 54-61.
Kozlov, A. V., Gille, L., Staniek, K. and Nohl, H. (1999) Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-elec
Kune, G. A., Bannerman, S., Field, B., Watson, L. F., Cleland, H., Merenstein, D. and Vitetta, L. (1992) Diet, alcohol, smoking, serum beta-carotene, and vitamin A in male nonmelanocytic skin cancer patients and controls. Nutr Cancer. 18, 237-44.
Le Bon, A. M. and Siess, M. H. (2000) Organosulfur compounds from Allium and the chemoprevention of cancer. Drug Metabol Drug Interact. 17, 51-79.
Liebler, D. C. and Burr, J. A. (2000) Antioxidant reactions of alpha-tocopherolhydroquinone. Lipids. 35, 1045-7.
Li, J., Chen, H., Tang, M. S., Shi, X., Amin, S., Desai, D., Costa, M. and Huang, C. (2004) PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells. J Cell Biol. 165, 77-86.
Li, J. P., Lin, J. C. and Yang, J. L. (2006) ERK activation in arsenite-treated G1-enriched CL3 cells contributes to survival, DNA repair inhibition, and micronucleus formation. Toxicol Sci. 89, 164-72.
Lii, C. K., Tsai, C. W. and Wu, C. C. (2006) Garlic allyl sulfides display differential modulation of rat cytochrome P450 2B1 and the placental form glutathione S-transferase in various organs. J Agric Food Chem. 54, 5191-6.
Lin, A. N., Reimer, R. J. and Carter, D. M. (1988) Sulfur revisited. J Am Acad Dermatol. 18, 553-8.
Liu, S. L., Lin, X., Shi, D. Y., Cheng, J., Wu, C. Q. and Zhang, Y. D. (2002) Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways. Arch Biochem Biophys. 406, 173-82.
Long, D. J., 2nd, Gaikwad, A., Multani, A., Pathak, S., Montgomery, C. A., Gonzalez, F. J. and Jaiswal, A. K. (2002) Disruption of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene in mice causes myelogenous hyperplasia. Cancer Res. 62, 3030-6.
Long, D. J., 2nd, Waikel, R. L., Wang, X. J., Perlaky, L., Roop, D. R. and Jaiswal, A. K. (2000) NAD(P)H:quinone oxidoreductase 1 deficiency increases susceptibility to benzo(a)pyrene-induced mouse skin carcinogenesis. Cancer Res. 60, 5913-5.
Long, D. J., 2nd, Waikel, R. L., Wang, X. J., Roop, D. R. and Jaiswal, A. K. (2001) NAD(P)H:quinone oxidoreductase 1 deficiency and increased susceptibility to 7,12-dimethylbenz[a]-anthracene-induced carcinogenesis in mouse skin. J Natl Cancer Inst. 93, 1166-70.
Lu, S. C. (1999) Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J. 13, 1169-83.
Maczurek, A., Hager, K., Kenklies, M., Sharman, M., Martins, R., Engel, J., Carlson, D. A. and Munch, G. (2008) Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer''s disease. Adv Drug Deliv Rev. 60, 1463-70.
Mayne, S. T. (2003) Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr. 133 Suppl 3, 933S-940S.
Mechta-Grigoriou, F., Gerald, D. and Yaniv, M. (2001) The mammalian Jun proteins: redundancy and specificity. Oncogene. 20, 2378-89.
Meyer, U. A. (1996) Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm. 24, 449-59.
Michaud, D. S., Pietinen, P., Taylor, P. R., Virtanen, M., Virtamo, J. and Albanes, D. (2002) Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer. 87, 960-5.
Miller, A.B. (1990) Diet and cancer: a review. Acta Oncol. 29: 87-95
Mulcahy, R. T., Wartman, M. A., Bailey, H. H. and Gipp, J. J. (1997) Constitutive and beta-naphthoflavone-induced expression of the human gamma-glutamylcysteine synthetase heavy subunit gene is regulated by a distal antioxidant response element/TRE sequence. J Biol Chem. 272, 7445-54.
Myzak, M. C. and Dashwood, R. H. (2006) Chemoprotection by sulforaphane: keep one eye beyond Keap1. Cancer Lett. 233, 208-18.
Nioi, P. and Hayes, J. D. (2004) Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors. Mutat Res. 555, 149-71.
Novotny, L., Rauko, P. and Cojocel, C. (2008) alpha-Lipoic acid: the potential for use in cancer therapy. Neoplasma. 55, 81-6.
O''Brien, M. L. and Tew, K. D. (1996) Glutathione and related enzymes in multidrug resistance. Eur J Cancer. 32A, 967-78.
Ohta, K., Ohigashi, M., Naganawa, A., Ikeda, H., Sakai, M., Nishikawa, J., Imagawa, M., Osada, S. and Nishihara, T. (2007) Histone acetyltransferase MOZ acts as a co-activator of Nrf2-MafK and induces tumour marker gene expression during hepatocarcinogenesis. Biochem J. 402, 559-66.
Okuda, A., Imagawa, M., Maeda, Y., Sakai, M. and Muramatsu, M. (1989) Structural and functional analysis of an enhancer GPEI having a phorbol 12-O-tetradecanoate 13-acetate responsive element-like sequence found in the rat glutathione transferase P gene. J Biol Chem. 264, 16919-26.
Packer, L., Witt, E. H. and Tritschler, H. J. (1995) alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 19, 227-50.
Paez, J. and Sellers, W. R. (2003) PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res. 115, 145-67.
Pan, S. Y., Ugnat, A. M., Mao, Y., Wen, S. W. and Johnson, K. C. (2004) A case-control study of diet and the risk of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 13, 1521-7.
Parcell, S. (2002) Sulfur in human nutrition and applications in medicine. Altern Med Rev. 7, 22-44.
Park, S. J., Zhao, H., Spitz, M. R., Grossman, H. B. and Wu, X. (2003) An association between NQO1 genetic polymorphism and risk of bladder cancer. Mutat Res. 536, 131-7.
Powis, G., Svingen, B. A. and Appel, P. (1981) Quinone-stimulated superoxide formation by subcellular fractions, isolated hepatocytes, and other cells. Mol Pharmacol. 20, 387-94.
Reddy, S. P. and Mossman, B. T. (2002) Role and regulation of activator protein-1 in toxicant-induced responses of the lung. Am J Physiol Lung Cell Mol Physiol. 283, L1161-78.
Reed, L. J. (1998) From lipoic acid to multi-enzyme complexes. Protein Sci. 7, 220-4.
Reed, L. J., De, B. B., Gunsalus, I. C. and Hornberger, C. S., Jr. (1951) Crystalline alpha-lipoic acid; a catalytic agent associated with pyruvate dehydrogenase. Science. 114, 93-4.
Reed, L. J. (2001) A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes. J Biol Chem. 276, 38329-36.
Roy, S. and Packer, L. (1998) Redox regulation of cell functions by alpha-lipoate: biochemical and molecular aspects. Biofactors. 7, 263-7. Ruhnau, K. J., Meissner, H. P., Finn, J. R., Reljanovic, M., Lobisch, M., Schutte, K., Nehrdich, D., Tritschler, H. J., Mehnert, H. and Ziegler, D. (1999) Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 16, 1040-3.
Rushmore, T. H. and Kong, A. N. (2002) Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Curr Drug Metab. 3, 481-90.
Sakamoto, K., Lawson, L. D. and Milner, J. A. (1997) Allyl sulfides from garlic suppress the in vitro proliferation of human A549 lung tumor cells. Nutr Cancer. 29, 152-6.
Sato, K. (1989) Glutathione transferases as markers of preneoplasia and neoplasia. Adv Cancer Res. 52, 205-55.
Sato, T. and Miyata, G. (2000) The nutraceutical benefit, part iv: garlic. Nutrition. 16, 787-8.
Satoh, K., Kitahara, A., Soma, Y., Inaba, Y., Hatayama, I. and Sato, K. (1985) Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis. Proc Natl Acad Sci U S A. 82, 3964-8.
Schaeffer, H. J. and Weber, M. J. (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol. 19, 2435-44.
Scheid, M. P. and Woodgett, J. R. (2003) Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett. 546, 108-12.
Schulz, W. A., Krummeck, A., Rosinger, I., Eickelmann, P., Neuhaus, C., Ebert, T., Schmitz-Drager, B. J. and Sies, H. (1997) Increased frequency of a null-allele for NAD(P)H: quinone oxidoreductase in patients with urological malignancies. Pharmacogenetics. 7, 235-9.
Seow, A., Yuan, J. M., Sun, C. L., Van Den Berg, D., Lee, H. P. and Yu, M. C. (2002) Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study. Carcinogenesis. 23, 2055-61.
Sheen, L. Y., Lii, C. K., Sheu, S. F., Meng, R. H. and Tsai, S. J. (1996) Effect of the active principle of garlic--diallyl sulfide--on cell viability, detoxification capability and the antioxidation system of primary rat hepatocytes. Food Chem Toxicol. 34, 971-8.
Shi, D. Y., Liu, H. L., Stern, J. S., Yu, P. Z. and Liu, S. L. (2008) Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway. FEBS Lett. 582, 1667-71.
Shih, P. H., Yeh, C. T. and Yen, G. C. (2007) Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis. J Agric Food Chem. 55, 9427-35.
Shimada, T. (2006) Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet. 21, 257-76.
Singh, U. and Jialal, I. (2008) Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 66, 646-57.
Strange, R. C., Spiteri, M. A., Ramachandran, S. and Fryer, A. A. (2001) Glutathione-S-transferase family of enzymes. Mutat Res. 482, 21-6.
Sundaram, S. G. and Milner, J. A. (1996) Diallyl disulfide induces apoptosis of human colon tumor cells. Carcinogenesis. 17, 669-73.
Surh, Y. J. (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 3, 768-80.
Talalay, P., Fahey, J. W., Holtzclaw, W. D., Prestera, T. and Zhang, Y. (1995) Chemoprotection against cancer by phase 2 enzyme induction. Toxicol Lett. 82-83, 173-9.
Testa, J. R. and Bellacosa, A. (2001) AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A. 98, 10983-5.
Tew, K. D. (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res. 54, 4313-20.
Torii, S., Yamamoto, T., Tsuchiya, Y. and Nishida, E. (2006) ERK MAP kinase in G cell cycle progression and cancer. Cancer Sci. 97, 697-702.
Townsend, D. M., Tew, K. D. and Tapiero, H. (2004) Sulfur containing amino acids and human disease. Biomed Pharmacother. 58, 47-55.
Tsai, C. W., Chen, H. W., Yang, J. J., Sheen, L. Y. and Lii, C. K. (2007) Diallyl disulfide and diallyl trisulfide up-regulate the expression of the pi class of glutathione S-transferase via an AP-1-dependent pathway. J Agric Food Chem. 55, 1019-26.
Tsai, C. W., Yang, J. J., Chen, H. W., Sheen, L. Y. and Lii, C. K. (2005) Garlic organosulfur compounds upregulate the expression of the pi class of glutathione S-transferase in rat primary hepatocytes. J Nutr. 135, 2560-5.
van Iersel, M. L., Verhagen, H. and van Bladeren, P. J. (1999) The role of biotransformation in dietary (anti)carcinogenesis. Mutat Res. 443, 259-70.
Wada, H., Shintani, D. and Ohlrogge, J. (1997) Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production. Proc Natl Acad Sci U S A. 94, 1591-6.
Wagner, E. F. (2001) AP-1--Introductory remarks. Oncogene. 20, 2334-5.
Wang, L. I., Giovannucci, E. L., Hunter, D., Neuberg, D., Su, L. and Christiani, D. C. (2004) Dietary intake of Cruciferous vegetables, Glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population. Cancer Causes Control. 15, 977-85.
Wattenberg, L. W. (1992) Inhibition of carcinogenesis by minor dietary constituents. Cancer Res. 52, 2085s-2091s.
Wenzel, U., Nickel, A. and Daniel, H. (2005) alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation. Apoptosis. 10, 359-68.
Wollin, S. D. and Jones, P. J. (2003) Alpha-lipoic acid and cardiovascular disease. J Nutr. 133, 3327-30.
Wu, C. C., Sheen, L. Y., Chen, H. W., Kuo, W. W., Tsai, S. J. and Lii, C. K. (2002) Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. J Agric Food Chem. 50, 378-83.
Xu, C., Li, C. Y. and Kong, A. N. (2005) Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res. 28, 249-68.
Zhang, Y., Kensler, T. W., Cho, C. G., Posner, G. H. and Talalay, P. (1994) Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci U S A. 91, 3147-50.
Zhang, Y., Munday, R., Jobson, H. E., Munday, C. M., Lister, C., Wilson, P., Fahey, J. W. and Mhawech-Fauceglia, P. (2006) Induction of GST and NQO1 in cultured bladder cells and in the urinary bladders of rats by an extract of broccoli (Brassica oleracea italica) sprouts. J Agric Food Chem. 54, 9370-6.
Zhang, Y., Talalay, P., Cho, C. G. and Posner, G. H. (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 89, 2399-403.
Ziegler, D., Hanefeld, M., Ruhnau, K. J., Meissner, H. P., Lobisch, M., Schutte, K. and Gries, F. A. (1995) Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia. 38, 1425-33.
Zhu, H., Jia, Z., Zhang, L., Yamamoto, M., Misra, H. P., Trush, M. A. and Li, Y. (2008) Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2 signaling and protection against oxidative and electrophilic stress. Exp Biol Med (Maywood). 233, 463-74.

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