title: A conjugate of doxorubicin and an analog of Luteinizing Hormone-Releasing Hormone shows increased efficacy against oral and laryngeal cancers.
abstract: A doxorubicin and [D-Lys(6)]Luteinizing Hormone-Releasing Hormone (LH-RH) conjugate, AN-152, was designed to target LH-RH receptor positive cells. AN-152 is more potent against a specific group of cancers than doxorubicin and has less peripheral toxicity. This therapy is potentially efficacious against many other types of malignancies. Here, AN-152 was tested on oral (KB) and laryngeal (HEp-2) carcinoma cells. LH-RH receptor presence was demonstrated by displacement binding assays. Cells were treated with 10 nM EGF or left untreated, then exposed to 0-10 microM AN-152. Cytotoxicity was assessed by MTT assay to determine ED(50) values. AN-152 association with the cells was monitored using two-photon laser scanning microscopy. AN-152 was more potent than doxorubicin in both KB and HEp-2 cell lines (P<0.05). Up-regulation of LH-RH receptors by epidermal growth factor (EGF) increased the entry and potency of AN-152 in KB cells, but not in HEp-2 cells. This novel approach may be effective against a variety of cancers.
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy*; D009062:Mouth Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
chemical_list: C080883:LHRH, lysine(6)-doxorubicin; D007987:Gonadotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D004317:Doxorubicin