Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties
Journal
Oncogene
Journal Volume
16
Journal Issue
22
Pages
2855-2863
Date Issued
1998
Author(s)
Abstract
We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185(neu) 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 p185(neu) 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 p185(neu) 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.
Subjects
Anthraquinone; Emodin; Experimental metastasis; HER-2/neur; Tyrosine kinase
SDGs
Other Subjects
carbonyl derivative; emodin; hydroxyl group; methyl group; protein tyrosine kinase; protein tyrosine kinase inhibitor; animal cell; article; breast cancer; cell proliferation; cell strain 3T3; chemical structure; controlled study; human; human cell; malignant transformation; metastasis; mouse; nonhuman; oncogene neu; phenotype; priority journal; Animalia
Publisher
Nature Publishing Group
Type
journal article