|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2008-1-23
|
|
pubmed:abstractText |
We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF-1 receptor (IGF-1R) and the HER2 receptor in breast cancer cells. Herein, we studied the effects of NDGA on the growth of estrogen receptor (ER) positive MCF-7 cells engineered to overexpress HER2 (MCF-7/HER2-18). These cells are an in vitro model of HER2-driven, ER positive, tamoxifen resistant breast cancer. NDGA was equally effective at inhibiting the growth of both parental MCF-7 and MCF-7/HER2-18 cells. Half maximal effects for both cell lines were in the 10-15 microM range. The growth inhibitory effects of NDGA were associated with an S phase arrest in the cell cycle and the induction of apoptosis. NDGA inhibited both IGF-1R and HER2 kinase activities in these breast cancer cells. In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF-1R inhibitor, was more effective in MCF-7/HER2-18 cells than in the parental MCF-7 cells and IGF binding protein-3 (IGFBP-3) was more effective against MCF-7 cells compared to MCF-7/HER2-18. MCF-7/HER2-18 cells are known to be resistant to the effects of the estrogen receptor inhibitor, tamoxifen. Interestingly, NDGA not only inhibited the growth of MCF-7/HER2-18 on its own, but it also demonstrated additive growth inhibitory effects when combined with tamoxifen. These studies suggest that NDGA may have therapeutic benefits in HER2-positive, tamoxifen resistant, breast cancers in humans.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/ERBB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nordihydroguaiaretic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Selective Estrogen Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/gefitinib
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1097-4644
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
(c) 2007 Wiley-Liss, Inc.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
103
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
624-35
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:17562544-Adenocarcinoma,
pubmed-meshheading:17562544-Antineoplastic Agents,
pubmed-meshheading:17562544-Antineoplastic Agents, Hormonal,
pubmed-meshheading:17562544-Apoptosis,
pubmed-meshheading:17562544-Breast Neoplasms,
pubmed-meshheading:17562544-Cell Division,
pubmed-meshheading:17562544-Cell Line, Tumor,
pubmed-meshheading:17562544-Drug Screening Assays, Antitumor,
pubmed-meshheading:17562544-Drug Synergism,
pubmed-meshheading:17562544-Female,
pubmed-meshheading:17562544-Humans,
pubmed-meshheading:17562544-Insulin-Like Growth Factor Binding Protein 3,
pubmed-meshheading:17562544-Neoplasm Proteins,
pubmed-meshheading:17562544-Neoplasms, Hormone-Dependent,
pubmed-meshheading:17562544-Nordihydroguaiaretic Acid,
pubmed-meshheading:17562544-Phosphorylation,
pubmed-meshheading:17562544-Protein Kinase Inhibitors,
pubmed-meshheading:17562544-Protein Processing, Post-Translational,
pubmed-meshheading:17562544-Quinazolines,
pubmed-meshheading:17562544-Receptor, IGF Type 1,
pubmed-meshheading:17562544-Receptor, erbB-2,
pubmed-meshheading:17562544-Selective Estrogen Receptor Modulators,
pubmed-meshheading:17562544-Tamoxifen
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells.
|
|
pubmed:affiliation |
Diabetes and Endocrine Research, University of California, San Francisco/Mt. Zion Medical Center, San Francisco, California, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
