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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Food Processing and Sensory Quality Research » Research » Publications at this Location » Publication #313014
Title: Antiestrogenic activity of flavnoid phytochemicals mediated via c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha

Author
item COLLINS-BUROW, BRIDGETTE - Tulane University
item ANTOON, JAMES - Tulane University
item FRIGO, DANIEL - University Of Houston
item ELLIOT, STEVEN - Tulane University
item WELDON, CHRISTOPHER - Harvard University
item Boue, Stephen
item BECKMAN, BARBARA - Tulane University
item CURIEL, TYLER - University Of Texas At San Antonio
item ALAM, JAWED - Tulane University
item BUROW, MATTHEW - Tulane University

Submitted to: The Journal of Steroid Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2012
Publication Date: 10/15/2012
Citation: Collins-Burow, B.M., Antoon, J.W., Frigo, D.E., Elliot, S., Weldon, C.B., Boue, S.M., Beckman, B.S., Curiel, T.J., Alam, J., Burow, M.E. 2012. Antiestrogenic activity of flavnoid phytochemicals mediated via c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha. The Journal of Steroid Biochemistry and Molecular Biology. 132:186-193.

Interpretive Summary: Flavonoid phytochemicals act as both agonists and antagonists of the human estrogen receptors. While a number of these compounds act by directly binding to the estrogen receptor, certain phytochemicals, such as the plant compounds chalcone and flavone, elicit antagonistic effects on estrogen signaling independent of direct receptor binding. Here we demonstrate both chalcone and flavone function as cell type-specific selective estrogen receptor modulators. In breast cancer cells chalcone and flavone suppress estrogen receptor (alpha) activity through activation of several proteins. Our results demonstrate a role for stress-activated kinases in the cell regulation of estrogen receptor (alpha) function.

Technical Abstract: Flavonoid phytochemicals act as both agonists and antagonists of the human estrogen receptors (ERs). While a number of these compounds act by directly binding to the ER, certain phytochemicals, such as the flavonoid compounds chalcone and flavone, elicit antagonistic effects on estrogen signaling independent of direct receptor binding. Here we demonstrate both chalcone and flavone function as cell type-specific selective ER modulators. In MCF-7 breast carcinoma cells chalcone and flavone suppress ERa activity through stimulation of the stress-activated members of the mitogen-activated protein kinase (MAPK) family: c-Jun N-terminal kinase (JNK)1 and JNK2. The use of dominant-negative mutants of JNK1 or JNK2 in stable transfected cells established that the antiestrogenic effects of chalcone and flavone required intact JNK signaling. We further show that constitutive activation of the JNK pathway partially suppresses estrogen (E2)-mediated gene expression in breast, but not endometrial carcinoma cells. Our results demonstrate a role for stress-activated MAPKs in the cell type-specific regulation of ERa function.