Publication Type:

Journal Article


Acta Pharmacologica Sinica, Volume 31, Number 9, p.1223-1240 (2010)



activating transcription factor 2, animal experiment, animal model, Animals, Anticarcinogenic Agents, Antineoplastic Combined Chemotherapy Protocols, article, binding site, Binding Sites, bioinformatics, C57BL 6 mouse, cancer cell, Catechin, Cell Line, Cell Survival, cell viability, chemoprophylaxis, controlled study, down regulation, epigallocatechin gallate, gene control, gene expression, Gene Expression Regulation, Genetic, human, human cell, Humans, in vitro study, in vivo study, Inbred C57BL, Knockout, luciferase, male, Mice, microarray analysis, mouse, Neoplastic, NF-E2-Related Factor 2, nonhuman, promoter region, Promoter Regions, prostate, prostate cancer, Prostatic Neoplasms, Protein Binding, protein protein interaction, real time polymerase chain reaction, reporter gene, sulforaphane, tea, Thiocyanates, transcription factor AP 1, Transcription Factor AP-1, transcription factor Elk 1, transcription factor Nrf2, Tumor


Aim:To examine the regulatory crosstalk between the transcription factors Nrf2 and AP-1 in prostate cancer (PCa) by dietary cancer chemopreventive compounds ()epigallocatechin-3-gallate (EGCG) from green tea and sulforaphane (SFN) from cruciferous vegetables.Methods:We performed (i) in vitro studies including luciferase reporter gene assays, MTS cell viability assays, and quantitative real-time PCR (qRT-PCR) in PC-3 AP-1 human PCa cells, (ii) in vivo temporal (3 h and 12 h) microarray studies in the prostate of Nrf2-deficient mice that was validated by qRT-PCR, and (iii) in silico bioinformatic analyses to delineate conserved Transcription Factor Binding Sites (TFBS) in the promoter regions of Nrf2 and AP-1, as well as coregulated genes including ATF-2 and ELK-1.Results:Our study shows that AP-1 activation was attenuated by the combinations of SFN (25 mol/L) and EGCG (20 or 100 mol/L) in PC-3 cells. Several key Nrf2-dependent genes were down-regulated (3-fold to 35-fold) after in vivo administration of the combination of EGCG (100 mg/kg) and SFN (45 mg/kg). Conserved TFBS signatures were identified in the promoter regions of Nrf2, AP-1, ATF2, and ELK-1 suggesting a potential regulatory mechanism of crosstalk between them.Conclusion:Taken together, our present study of transcriptome profiling the gene expression changes induced by dietary phytochemicals SFN and EGCG in Nrf2-deficient mice and in PC-3 cells in vitro demonstrates that the effects of SFN+EGCG could be mediated via concerted modulation of Nrf2 and AP-1 pathways in the prostate. © 2010 CPS and SIMM All rights reserved.


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Cite this Research Publication

Sab c d Nair, Barve, Aa, Khor, T. - Oa, Shen, G. - Xa, Lin, Wa, Chan, J. Ye, Cai, Lf, and Kong, A. - Na, “Regulation of Nrf2-and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells”, Acta Pharmacologica Sinica, vol. 31, pp. 1223-1240, 2010.