New Insight into Oncoprotein-Targeted Antitumor Effect: Herbimycin a as an Antagonist of Protein Tyrosine Kinase against Ph¹-Positive Leukemia Cells

Abstract

Herbimycin A, a benzoquinonoid anasamycin antibiotic, has been shown to reserve the oncogenic phenotypes of p60^v-src transformed cells by the virtue of the inhibition of src protein tyrosine kinase. Furthermore, we previously demonstrated that herbimycin A displayed the antitumor activity on Ph¹-positive leukemia cells and bcr/abl oncoprotein-associated transformed murine hematopoietic cells with the transfection of a retroviral vector expressing bcr/abl. Herbimycin A showed preferential inhibition on the in vitro growth of Ph¹-positive leukemia cells and bcr/abl oncoprotein-associated murine hematopoietic cells through the inhibition of bcr/abl tyrosine kinase activity and the reduction of subsequent phosphotyrosyl proteins. Recently, from the view of investigating the oncogenic significance or of developing a future clinical application in malignancies, several developing agents targeted against oncoprotein have been tried. We reviewed the present progress in the mechanism of oncoprotein-targeted antitumor effects and focused on herbimycin A-induced antitumor activity on Ph¹-positive leukemia cells.

Key Words:

• Ph¹-positive leukemia
• Herbimycin A
• Inhibitor of tyrosine kinase
• bcr/abl Oncoprotein
• Phosphotyrosine
• Antisense oligodeoxynucleotides