Targeted enhancement of the biological activity of the antineoplastic agent, neocarzinostatin. Studies in murine neuroblastoma cells.

Abstract

The development of chemotherapeutic approaches to cancer has been hampered by the toxicity of proposed agents for normal rapidly dividing cells. By using neocarzinostatin, a "pro-drug" which is activated by reduction by thiol compounds, adjunctively with 6-mercaptodopamine, a thiol-containing dopamine analogue, we have been able to enhance neocarzinostatin toxicity for cells of the neural crest tumor neuroblastoma. Thiol compounds that are not neurotransmitter analogues do not act synergistically with neocarzinostatin in this system. Since most normal rapidly dividing cells do not have surface dopamine receptors, we propose this approach for the selective targeting of toxicity for neuroblastoma cells. We further introduce cell-selective activation of prodrugs as a new chemotherapeutic strategy which demands further development.