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Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells.
J Cell Biochem. 2008 Feb 01; 103(2):624-35.JC

Abstract

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.

Authors+Show Affiliations

Diabetes and Endocrine Research, University of California, San Francisco/Mt. Zion Medical Center, San Francisco, California, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17562544

Citation

Zavodovskaya, Marianna, et al. "Nordihydroguaiaretic Acid (NDGA), an Inhibitor of the HER2 and IGF-1 Receptor Tyrosine Kinases, Blocks the Growth of HER2-overexpressing Human Breast Cancer Cells." Journal of Cellular Biochemistry, vol. 103, no. 2, 2008, pp. 624-35.
Zavodovskaya M, Campbell MJ, Maddux BA, et al. Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. J Cell Biochem. 2008;103(2):624-35.
Zavodovskaya, M., Campbell, M. J., Maddux, B. A., Shiry, L., Allan, G., Hodges, L., Kushner, P., Kerner, J. A., Youngren, J. F., & Goldfine, I. D. (2008). Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. Journal of Cellular Biochemistry, 103(2), 624-35.
Zavodovskaya M, et al. Nordihydroguaiaretic Acid (NDGA), an Inhibitor of the HER2 and IGF-1 Receptor Tyrosine Kinases, Blocks the Growth of HER2-overexpressing Human Breast Cancer Cells. J Cell Biochem. 2008 Feb 1;103(2):624-35. PubMed PMID: 17562544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. AU - Zavodovskaya,Marianna, AU - Campbell,Michael J, AU - Maddux,Betty A, AU - Shiry,Laura, AU - Allan,Geoffrey, AU - Hodges,Leslie, AU - Kushner,Peter, AU - Kerner,John A, AU - Youngren,Jack F, AU - Goldfine,Ira D, PY - 2007/6/15/pubmed PY - 2008/5/2/medline PY - 2007/6/15/entrez SP - 624 EP - 35 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 103 IS - 2 N2 - 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. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/17562544/Nordihydroguaiaretic_acid__NDGA__an_inhibitor_of_the_HER2_and_IGF_1_receptor_tyrosine_kinases_blocks_the_growth_of_HER2_overexpressing_human_breast_cancer_cells_ L2 - https://doi.org/10.1002/jcb.21435 DB - PRIME DP - Unbound Medicine ER -