title: Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog, AN-162 (AEZS-124), and its effects on tumor growth inhibition.
abstract: In view of findings that various tumors express receptors for somatostatin, a new targeted cytotoxic analog of somatostatin, AN-162 (AEZS-124), consisting of doxorubicin linked through glutaric acid to the somatostatin octapeptide RC-121 was developed in our laboratory. We studied the toxicity in vivo and the effect of AN-162 on growth of the MDA-MB-231 estrogen-independent human breast cancer cell line xenografted into nude mice. AN-162 induced significant tumor growth inhibition compared with the control and the group treated with doxorubicin in equimolar doses. We also evaluated the stability of AN-162 in various sera in vitro, as this conjugate is susceptible to hydrolysis by serum carboxylesterase enzymes in the circulation. This study shows for the first time that AN-162 is a safe and effective compound for the treatment of experimental breast cancer. Our findings support the concept of targeted chemotherapy based on cytotoxic peptide analog AN-162 for the treatment of breast cancers and other cancers expressing somatostatin receptors.
authors.affiliation: Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center Florida, South Florida VA Foundation for Research and Education, Florida, USA. steph-seitz@t-online.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Seitz
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Andrea
authors.initials: A
authors.lastname: Treszl
authors.forename: Andrea
authors.initials: A
authors.lastname: Papadia
authors.forename: Ferenc
authors.initials: F
authors.lastname: Rick
authors.forename: Luca
authors.initials: L
authors.lastname: Szalontay
authors.forename: Karoly
authors.initials: K
authors.lastname: Szepeshazi
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
authors.forename: Gabor
authors.initials: G
authors.lastname: Halmos
authors.forename: Florian
authors.initials: F
authors.lastname: Hohla
authors.forename: Stefan
authors.initials: S
authors.lastname: Buchholz
mesh_terms: D015078:2-Hydroxyphenethylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000814:Aniline Compounds / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D043182:Carboxylesterase / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008819:Mice, Nude; D013004:Somatostatin / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; C000956:N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline; D013004:Somatostatin; D015078:2-Hydroxyphenethylamine; D004317:Doxorubicin; D043182:Carboxylesterase