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Tumor Biology

Suppressed Transformation and Induced Differentiation of HER-2/neu-overexpressing Breast Cancer Cells by Emodin

Lisha Zhang, Ching-jer Chang, Sarah S. Bacus and Mien-Chie Hung
Lisha Zhang
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Ching-jer Chang
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Sarah S. Bacus
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Mien-Chie Hung
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DOI:  Published September 1995
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Abstract

The amplification and overexpression of the HER-2/neu proto-oncogene, which encodes the tyrosine kinase receptor p185neu, have been observed frequently in tumors from human breast cancer patients and are correlated with poor prognosis. To explore the potential of chemotherapy directed at the tyrosine kinase of p185neu, we have found that emodin (3-methyl-1,6,8-trihydroxyanthraquinone), a tyrosine kinase inhibitor, suppresses autophosphorylation and transphosphorylation activities of HER-2/neu tyrosine kinase, resulting in tyrosine hypophosphorylation of p185neu in HER-2/neu-overexpressing breast cancer cells. Emodin, at a 40-µm concentration, which repressed tyrosine kinase of p185neu, efficiently inhibited both anchorage-dependent and anchorage-independent growth of HER-2/neu-overexpressing breast cancer cells. However, the inhibition was much less effective for those cells expressing basal levels of p185neu under the same conditions. Emodin also induced differentiation of HER-2/neu-overexpressing breast cancer cells by exhibiting a morphological maturation property of large lacy nuclei surrounded by sizable flat cytoplasm and by showing a measurable production of large lipid drop-lets, which is a marker of mature breast cells. Therefore, our results indicate that emodin inhibits HER-2/neu tyrosine kinase activity and preferentially suppresses growth and induces differentiation of HER-2/neu-overexpressing cancer cells. These results may have chemotherapeutic implications for using emodin to target HER-2/neu-overexpressing cancer cells.

Footnotes

  • ↵1 This study was supported by National Institutes of Health Grants CA 58880 and CA 60856 (to M-C. H.) and CA 50743 (to C-j. C.), United States Army Grant DAMD 17-94-J-4315 (to M-C. H.), and a grant from Becton Dickinson Cellular Imaging Systems (to S. S. B.).

  • ↵2 To whom request for reprints should be addressed, at Department of Tumor Biology, Box 79, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

  • Received March 28, 1995.
  • Accepted June 30, 1995.
  • ©1995 American Association for Cancer Research.
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September 1995
Volume 55, Issue 17
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Suppressed Transformation and Induced Differentiation of HER-2/neu-overexpressing Breast Cancer Cells by Emodin
Lisha Zhang, Ching-jer Chang, Sarah S. Bacus and Mien-Chie Hung
Cancer Res September 1 1995 (55) (17) 3890-3896;

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Suppressed Transformation and Induced Differentiation of HER-2/neu-overexpressing Breast Cancer Cells by Emodin
Lisha Zhang, Ching-jer Chang, Sarah S. Bacus and Mien-Chie Hung
Cancer Res September 1 1995 (55) (17) 3890-3896;
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