Title |
Nordihydroguaiaretic Acid (NDGA) Inhibits the IGF-1 and c-erbB2/HER2/neu Receptors and Suppresses Growth in Breast Cancer Cells
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Published in |
Breast Cancer Research and Treatment, November 2005
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DOI | 10.1007/s10549-005-6939-z |
Pubmed ID | |
Authors |
Jack F. Youngren, Karissa Gable, Cristina Penaranda, Betty A. Maddux, Marianna Zavodovskaya, Margaret Lobo, Michael Campbell, John Kerner, Ira D. Goldfine |
Abstract |
Nordihydroguaiaretic acid (NDGA) is a phenolic compound isolated from the creosote bush Larrea divaricatta that has anti-cancer activities both in vitro and in vivo. We can now attribute certain of these anti-cancer properties in breast cancer cells to the ability of NDGA to directly inhibit the function of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu (HER2/neu) receptor. In MCF-7 human breast cancer cells, low micromolar concentrations of NDGA inhibited activation of the IGF-1R, and downstream phosphorylation of both the Akt/PKB serine kinase and the pro-apoptotic protein BAD. In mouse MCNeuA cells, NDGA also inhibited ligand independent phosphorylation of HER2/neu. To study whether this inhibitory effect in cells was due to a direct action on these receptors, we studied the IGF-1-stimulated tyrosine kinase activity of isolated IGF-1R, which was inhibited by NDGA at 10 muM or less. NDGA was also effective at inhibiting autophosphorylation of the isolated HER2/neu receptor at similar concentrations. In addition, NDGA inhibited IGF-1 specific growth of cultured breast cancer cells with an IC50 of approximately 30 muM. NDGA treatment (intraperitoneal injection 3 times per week) also decreased the activity of the IGF-1R and the HER2/neu receptor in MCNeuA cells implanted into mice. This inhibition of RTK activity was associated with decreased growth rates of MCNeuA cells in vivo. These studies indicate that the anti-breast cancer properties of NDGA are related to the inhibition of two important RTKs. Agents of this class may therefore provide new insights into potential therapies for this disease. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 3% |
Unknown | 35 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 11 | 31% |
Student > Ph. D. Student | 6 | 17% |
Professor | 4 | 11% |
Student > Master | 3 | 8% |
Student > Bachelor | 2 | 6% |
Other | 8 | 22% |
Unknown | 2 | 6% |
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Medicine and Dentistry | 8 | 22% |
Biochemistry, Genetics and Molecular Biology | 4 | 11% |
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Psychology | 2 | 6% |
Other | 7 | 19% |
Unknown | 3 | 8% |