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

Leuk Res. 1994 Mar;18(3):213-20. doi: 10.1016/0145-2126(94)90117-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Benzoquinones
  • Fusion Proteins, bcr-abl / metabolism
  • Genistein
  • Humans
  • Isoflavones / pharmacology
  • Lactams, Macrocyclic
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Neoplasm Proteins / metabolism*
  • Phosphotyrosine
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinones / pharmacology*
  • Rifabutin / analogs & derivatives
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Benzoquinones
  • Isoflavones
  • Lactams, Macrocyclic
  • Neoplasm Proteins
  • Quinones
  • Rifabutin
  • Phosphotyrosine
  • Tyrosine
  • herbimycin
  • Genistein
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl