Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on growth of estrogen-independent MXT mouse mammary carcinoma in vivo.
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.
Szepeshazi
K
K
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA.
Schally
A V
AV
Juhasz
A
A
Nagy
A
A
Janaky
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000494:pharmacology*; D001665:Binding Sites; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010053:Ovary / Q000033:anatomy & histology; D011974:Receptors, LH / Q000378:metabolism; D017329:Triptorelin Pamoate; D014599:Uterus / Q000033:anatomy & histology
D000880:Anthraquinones; D011974:Receptors, LH; D017329:Triptorelin Pamoate; C076643:glutaryl-2-(hydroxymethyl)anthraquinone; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D013006:Growth Hormone; D008727:Methotrexate