Melanotropin–daunomycin conjugate shows receptor-mediated cytotoxicity in cultured murine melanoma cells

Abstract

MELANOTROPIN (MSH) binds to specific receptors at the surface of mouse melanoma cells, preferentially in the G–2 phase of the cell cycle¹. On prolonged incubation, a fluorescein–MSH conjugate is internalised and appears intracellularly in small vesicles². The same phenomenon has been demonstrated by electron microscopy with an MSH–ferritin–fluorescein conjugate³. Although a role for the internalisation of MSH receptors in the execution of the hormonal message is still open to question, the fact that these conjugates of MSH are specifically recognised and internalised by melanoma cells offers a possibility for specific, site-directed chemotherapy of melanomas. We have therefore assumed that MSH–toxin conjugates might be specifically recognised and internalised and thereby have a selective toxic effect on cells that display MSH receptors on their surface. Even though the principle of site-directed chemotherapy has been known for a long time, it is only recently that this field became active⁴. Conjugates of specific antibodies and cytotoxic substances^5–7, as well as a DNA–daunomycin complex⁸ have been used in an attempt to increase the selectivity of the toxic agents. In this report we describe the synthesis of a melanotropin–daunomycin conjugate and its MSH receptor mediated cytotoxic effect on mouse melanoma cells in vitro.