MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on November 2, 2005; DOI: 10.1124/mol.105.017053

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.105.017053v1
69/2/430    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riby, J. E
Right arrow Articles by Bjeldanes, L. F
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riby, J. E
Right arrow Articles by Bjeldanes, L. F


Received for publication July 21, 2005.
Revised October 6, 2005.
Accepted for publication November 1, 2005.

Activation and Potentiation of Interferon-{gamma} Signaling by 3,3'-Diindolylmethane in MCF-7 Breast Cancer Cells

Jacques E Riby 1, Ling Xue 1, Urmi Chatterji 1, Erik L. Bjeldanes 2, Gary L. Firestone 1, Leonard F Bjeldanes 1*

1 University of California at Berkeley 2 Incyte Genomics

* Address correspondence to: E-mail: lfb{at}nature.berkeley.edu

Abstract

3,3'-diindolylmethane (DIM), a natural autolytic product in plants of the Brassica genus including broccoli, cauliflower and Brussels sprouts, exhibits promising cancer protective activities, especially against mammary neoplasia in animal models. We observed previously that DIM induced a G1 cell-cycle arrest, and strong induction of cell-cycle inhibitor p21 expression and promoter activity in both estrogen responsive and estrogen independent breast cancer cell lines. We recently showed that DIM upregulates the expression of interferon gamma (IFN{gamma}) in human MCF-7 breast cancer cells. This novel effect may contribute to the anticancer effects of DIM since IFN{gamma} plays an important role in preventing the development of primary and transplanted tumors. In this study, we observed that DIM activated the IFN{gamma} signaling pathway in human breast cancer cells. DIM activated the expression of the IFN{gamma} receptor (IFNGR1) and IFN{gamma} responsive genes, p56 and p69-OAS. In cotreatments with IFN{gamma}, DIM produced an additive activation of endogenous p69-OAS and of an OAS-Luc reporter and a synergistic activation of a GAS-Luc reporter. DIM synergistically augmented the IFN{gamma} induced phosphorylation of the transcription factor STAT-1, further evidence of DIM activation of the IFN{gamma} pathway. DIM and IFN{gamma} produced an additive inhibition of cell proliferation and a synergistic increase in levels of major histocompatibility complex class-1 (MHC-I) expression, accompanied by increased levels of mRNAs of MHC-1 associated proteins and transporters. These results reveal novel immune activating and potentiating activities of DIM in human tumor cells that may contribute to the established effectiveness of this dietary indole against various tumors types.


Key words: Interferons, Jak/Stats, Stat activated transcriptional events, Transcriptional coactivators, Mechanisms of cell killing/apoptosis, Metastasis, Oncogenes, Angiogenesis


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
S. C. Tilton, J. D. Hendricks, G. A. Orner, C. B. Pereira, G. S. Bailey, and D. E. Williams
Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout
Carcinogenesis, July 1, 2007; 28(7): 1589 - 1598.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Chen, K. A. Durkin, and J. E. Casida
Spontaneous Mobility of GABAA Receptor M2 Extracellular Half Relative to Noncompetitive Antagonist Action
J. Biol. Chem., December 15, 2006; 281(50): 38871 - 38878.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics