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  • Title: Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on growth of estrogen-independent MXT mouse mammary carcinoma in vivo.
    Author: Szepeshazi K, Schally AV, Juhasz A, Nagy A, Janaky T.
    Journal: Anticancer Drugs; 1992 Apr; 3(2):109-16. PubMed ID: 1388062.
    Abstract:
    Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF1 mice bearing MXT ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a significant inhibition of tumor growth. The effects of T-98 and T-121/B were superior to those obtained by treatment with equimolar doses of cytotoxic moiety anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs have a combined hormonal and cytotoxic activity with a reduced toxicity after administration in vivo. This is the first demonstration of in vivo tumor inhibition by targeted LH-RH analogs bearing cytotoxic radicals.
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