QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frigo, D. E. Articles by Burow, M. E. Search for Related Content PubMed PubMed Citation Articles by Frigo, D. E. Articles by Burow, M. E.

---

Nutrient-Gene Expression

Flavonoid Phytochemicals Regulate Activator Protein-1 Signal Transduction Pathways in Endometrial and Kidney Stable Cell Lines¹

Environmental Endocrinology Laboratory, Center for Bioenvironmental Research, Tulane and Xavier Universities, ^* Molecular and Cellular Biology Program, Tulane Cancer Center, Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112

²To whom correspondence should be addressed. E-mail: mburow{at}tulane.edu.

Phytochemicals bind to and regulate the human estrogen receptors (ER and ERß), mimicking actions of the endogenous estrogen, 17ß-estradiol, and known antiestrogens such as ICI 182,780. Recently, however, some of these estrogenic phytochemicals have been shown to affect other signal transduction pathways, such as receptor tyrosine kinases and mitogen-activated protein kinases (MAPK). Previously, we found that certain phytochemicals, such as flavone, apigenin, kaempferide and chalcone, have potent antiestrogenic activity. However, the antiestrogenicity of these compounds does not correlate with their ER binding capacity, suggesting alternative signaling as a mechanism for their antagonistic effects. In this study, we examined the effects of these compounds on the transcription factor activator protein-1 (AP-1). Using AP-1-luciferase stable human endometrial adenocarcinoma Ishikawa and human embryonic kidney (HEK) 293 cells, chalcone, flavone and apigenin all stimulated AP-1 activity. Additionally, we determined the effects of the phytochemicals on transcription factors that are downstream targets of various MAPK pathways. To test this, we used HEK 293 cells stably cointegrated with GAL4 transcriptional activation systems of Elk-1, c-Jun or C/EBP homologous protein (CHOP). Chalcone was the only phytochemical that activated all three transcription factors [Elk-1, 2.7-fold (P < 0.001); c-Jun, 2.7-fold (P = 0.025); CHOP, 3.0-fold (P = 0.002)], whereas apigenin stimulated CHOP (3.9-fold; P < 0.001), but inhibited phorbol myristoyl acetate–induced c-Jun activity (71%;P = 0.006). This work suggests that phytochemicals affect multiple signaling pathways that converge at the level of transcriptional regulation. The ability of flavonoids to regulate MAPK-responsive pathways in a selective manner indicates a mechanism by which phytochemicals may influence human health and disease.

KEY WORDS: • flavonoid phytochemicals • estrogen receptor • mitogen-activated protein kinase • activator protein-1

This article has been cited by other articles:

				J. A. JOSEPH, B. SHUKITT-HALE, and F. C. LAU Fruit Polyphenols and Their Effects on Neuronal Signaling and Behavior in Senescence Ann. N.Y. Acad. Sci., April 1, 2007; 1100(1): 470 - 485. [Abstract] [Full Text] [PDF]

				D. E. Frigo, A. Basu, E. N. Nierth-Simpson, C. B. Weldon, C. M. Dugan, S. Elliott, B. M. Collins-Burow, V. A. Salvo, Y. Zhu, L. I. Melnik, et al. p38 Mitogen-Activated Protein Kinase Stimulates Estrogen-Mediated Transcription and Proliferation through the Phosphorylation and Potentiation of the p160 Coactivator Glucocorticoid Receptor-Interacting Protein 1 Mol. Endocrinol., May 1, 2006; 20(5): 971 - 983. [Abstract] [Full Text] [PDF]

				H. Abuarqoub, R. Foresti, C. J. Green, and R. Motterlini Heme oxygenase-1 mediates the anti-inflammatory actions of 2'-hydroxychalcone in RAW 264.7 murine macrophages Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1092 - C1099. [Abstract] [Full Text] [PDF]

				J. A Joseph, B. Shukitt-Hale, and G. Casadesus Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds Am. J. Clinical Nutrition, January 1, 2005; 81(1): 313S - 316S. [Abstract] [Full Text] [PDF]

				N. K. Basu, S. Kubota, M. R. Meselhy, M. Ciotti, B. Chowdhury, M. Hartori, and I. S. Owens Gastrointestinally Distributed UDP-glucuronosyltransferase 1A10, Which Metabolizes Estrogens and Nonsteroidal Anti-inflammatory Drugs, Depends upon Phosphorylation J. Biol. Chem., July 2, 2004; 279(27): 28320 - 28329. [Abstract] [Full Text] [PDF]

				D. E. Frigo, Y. Tang, B. S. Beckman, A. B. Scandurro, J. Alam, M. E. Burow, and J. A. McLachlan Mechanism of AP-1-mediated gene expression by select organochlorines through the p38 MAPK pathway Carcinogenesis, February 1, 2004; 25(2): 249 - 261. [Abstract] [Full Text] [PDF]

				R. Van Dross, Y. Xue, A. Knudson, and J. C. Pelling The Chemopreventive Bioflavonoid Apigenin Modulates Signal Transduction Pathways in Keratinocyte and Colon Carcinoma Cell Lines J. Nutr., November 1, 2003; 133(11): 3800S - 3804. [Abstract] [Full Text] [PDF]

				Y.-J. Choi, J.-S. Kang, J. H. Y. Park, Y.-J. Lee, J.-S. Choi, and Y.-H. Kang Polyphenolic Flavonoids Differ in Their Antiapoptotic Efficacy in Hydrogen Peroxide-Treated Human Vascular Endothelial Cells J. Nutr., April 1, 2003; 133(4): 985 - 991. [Abstract] [Full Text] [PDF]