SEQUENTIAL INHIBITION OF LACTIC DEHYDROGENASE ISOZYMES OF HUMAN BRAIN BY HONVAN (STILBOESTROL DIPHOSPHATE)(In vitro experiments)

Abstract

In vitro experiments demonstrated a competitive inhibitory effect of stilboestrol diphosphate (HONVAN, ASTA) on total LDH activity in brain extracts. Honvan in increasing concentrations caused a sequential inhibition of the individual LDH isozymes of normal brain and of malignant tumors in the direction from the slowest moving isozyme (band 5) towards the fastest moving. The LDH activity associated with band one appeared relatively unaffected by large doses of Honvan. Several theoretical biochemical aspects of the individual LDH isozymes were studied by means of the sequential inhibition by Honvan. Infrared analysis of brain extracts incubated with Honvan demonstrated the liberation of free stilbestrol from the diphosphate ester. The relation of the inhibitory effect of stilbestrol diphosphate to the slower, malignant LDH isozymes suggests that the cytostatic effect in the treatment of cancer with this drug is mainly or solely due to the blocking effect by free stilboestrol on this enzyme of the glycolytic pathway. These experiments indicate the possible use of Honvan and similar compounds on a broader scale as cytostatic agents.