Inhibition of v-fms-induced tumor growth in nude mice by castanospermine

Abstract

Castanospermine, an indolizidine alkaloid isolated from the seeds of the chestnut tree Castanospermum australe, has been shown to prevent the normal glycosylational processing of the v-fms-transforming glycoprotein. v-fms-transformed cells grown in vitro in the presence of castanospermine accumulate immature forms of the glycoprotein that do not reach the cell surface. These treated cells revert to the normal phenotype. We have now extended those studies to an in vivo tumorigenicity model in the nude mouse using v-fms-transformed rat cells (SM-FRE) and dietary administration of castanospermine. Following tumor induction with s.c. injection of 10(6) SM-FRE cells, mice whose diet had been supplemented with 2.4 mg castanospermine/g food consumed approximately 0.84 mg castanospermine/g mouse/day. Furthermore, these mice had slower growing tumors that were 2.6 times smaller than tumors in control groups at the termination of the experiment 24 days postinjection. These results indicate that castanospermine is effective in slowing the growth of v-fms-transformed cells in vivo, suggesting that this drug may offer an effective therapy against certain tumors, including some arising from activated protooncogenes that encode glycoproteins such as growth factor receptors.