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Effect of herbimycin A, an inhibitor of tyrosine kinase, on protein tyrosine kinase activity and phosphotyrosyl proteins of Ph1-positive leukemia cells.

Abstract
Herbimycin A, a benzoquinonoid anasamycin antibiotic, preferentially inhibited the in vitro growth of Ph1-positive leukemia cell lines. On the other hand, genistein, which was developed as an inhibitor of receptor-type tyrosine kinase, and other protein kinase inhibitors showed no selective inhibition of Ph1-positive leukemia cell growth. Herbimycin A also displayed an abrogative effect on the transformation of murine hematopoietic cells by transfection with a bcr/abl oncoprotein-expressing retroviral vector. The antitumor action of herbimycin A on Ph1-positive leukemia cells is related to an inhibition of activity of bcr/abl protein tyrosine kinase and a subsequent reduction of the constitutive phosphotyrosyl proteins, however, the antibiotic has no effect on the expression of bcr/abl mRNA and oncoprotein. Therefore, herbimycin A may provide an important insight into the oncogenic action of bcr/abl oncoprotein and the future development of oncoprotein-targeted therapeutic agents.
AuthorsM Okabe, K Kawamura, T Miyagishima, T Itaya, D Goodwyn, M Shoji, W R Vogler, K Sakurada, M Uehara, T Miyazaki
JournalLeukemia research (Leuk Res) Vol. 18 Issue 3 Pg. 213-20 (Mar 1994) ISSN: 0145-2126 [Print] England
PMID7511193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibiotics, Antineoplastic
  • Benzoquinones
  • Isoflavones
  • Lactams, Macrocyclic
  • Neoplasm Proteins
  • Quinones
  • Rifabutin
  • Phosphotyrosine
  • Tyrosine
  • herbimycin
  • Genistein
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Benzoquinones
  • Fusion Proteins, bcr-abl (metabolism)
  • Genistein
  • Humans
  • Isoflavones (pharmacology)
  • Lactams, Macrocyclic
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive (enzymology, metabolism, pathology)
  • Neoplasm Proteins (metabolism)
  • Phosphotyrosine
  • Protein-Tyrosine Kinases (antagonists & inhibitors)
  • Quinones (pharmacology)
  • Rifabutin (analogs & derivatives)
  • Tumor Cells, Cultured (drug effects, metabolism, pathology)
  • Tyrosine (analogs & derivatives, metabolism)

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