Thyrotropin-Daunomycin Conjugate Shows Receptor-Mediated Cytotoxicity in Cultured Thyroid Cells

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Abstract
Daunomycin (DM), a potent chemotherapeutic agent, was linked to bovine thyrotropin (TSH) directly (TSH-DM) and indirectly (TSH-.alpha.-lactalbumin-DM) by covalent cross-linking methods. The activity of these hormone-daunomycin conjugates was tested in vitro on the rabbit thyroid cells in primary culture. Both TSH-DM and TSH-.alpha.-lactalbumin-DM conjugates inhibited [3H]leucine incorporation and cell proliferation, while free TSH did not. Their inhibitory action was more potent than that of free daunomycin. The inhibition appeared to be specific to the thyroid cells and diminished in the presence of a large amount of free TSH, suggesting that the cytotoxic action of these TSH-DM conjugates was a receptor-mediated phenomenon. Hormone-cytotoxic drug conjugates may serve as a potent site-directed therapy for thyroid tumors.