CHAPTER 9 - Oncogene Function Inhibitors of Microbial Origin

Abstract

This chapter discusses the oncogene function inhibitors of microbial origin. Streptomyces and other microorganisms produce antibiotics, anticancer agents, and enzyme inhibitors as secondary metabolites. Therefore, microorganisms are a treasury of organic compounds that have various structures and biological activities. Isolation of the specific bioactive products in culture broths depends on the testing method. As oncogene theory has been extensively developed in the field of carcinogenesis research, oncogene function inhibitors have been screened as a new group of microbial secondary metabolites. The EGF-receptor-associated tyrosine kinase was reported to act in the sequential ordered bi–bi mechanism, in which the peptide comes first and ATP comes second to the enzyme active site. Kinetic studies using Lineweaver–Burk plotting indicated that lavendustin A inhibits the tyrosine kinase competitively with ATP and noncompetitively with the peptide substrate. The mechanism of inhibition is different from that of erbstatin, which competes with the peptide but is similar to that of orobol and genistein. Although lavendustin A is a potent inhibitor of tyrosine kinase in vitro , it did not show any biological effect in cultured cells.