Abstract
We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185neu receptor tyrosine kinase. In this study, we examine the relationship between the chemical structure and the activity of emodin and nine derivatives, and identified that one methyl, one hydroxy, and one carbonyl functional groups are critical for the biological activities of emodin. We also found that one of the derivatives 10-(4-acetamidobenzylidene)-9-anthrone (DK-V-47) is more effective than emodin in repressing the tyrosine phosphorylation of p185neu and in inhibiting the proliferation and transformation of HER-2/neu-overexpressing human breast cancer cells. Using mutation-activated HER-2/neu transformed 3T3 cells, we also investigated whether emodin and DK-V-47 can inhibit malignant transformation induced solely by the HER-2/neu oncogene. We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchorage-dependent and -independent growth, metastasis-associated properties. These results clearly indicate that the inhibition of p185neu tyrosine kinase by both emodin and DK-V-47 is capable of suppressing the HER-2/neu associated transformed phenotypes including the ability to induce metastatic potential. Our results also support the chemotherapeutic implications of the use of either emodin or DK-V-47 to target HER-2/neu-overexpressing cancer cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zhang, L., Lau, YK., Xi, L. et al. Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene 16, 2855–2863 (1998). https://doi.org/10.1038/sj.onc.1201813
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201813
Keywords
This article is cited by
-
Rheum australe, an endangered high-value medicinal herb of North Western Himalayas: a review of its botany, ethnomedical uses, phytochemistry and pharmacology
Phytochemistry Reviews (2018)
-
Medicinal plants of Ecuador: a review of plants with anticancer potential and their chemical composition
Medicinal Chemistry Research (2015)
-
Emodin can induce K562 cells to erythroid differentiation and improve the expression of globin genes
Molecular and Cellular Biochemistry (2013)
-
Emodin–phospholipid complex
Journal of Thermal Analysis and Calorimetry (2012)
-
Inhibition of DNA topoisomerases I and II of compounds from Reynoutria japonica
Archives of Pharmacal Research (2012)