Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog, AN-162 (AEZS-124), and its effects on tumor growth inhibition

Stephan Seitz, Andrew V. Schally, Andrea Treszl, Andrea Papadia, Ferenc Rick, Luca Szalontay, Karoly Szepeshazi, Olaf Ortmann, Gabor Halmos, Florian Hohla, Stefan Buchholz

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)553-558
Number of pages6
JournalAnti-cancer drugs
Volume20
Issue number7
DOIs
StatePublished - Sep 28 2009

Keywords

  • AN-162
  • Breast cancer
  • Doxorubicin
  • Half-life
  • Somatostatin
  • Targeted therapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research
  • Oncology

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    Seitz, S., Schally, A. V., Treszl, A., Papadia, A., Rick, F., Szalontay, L., Szepeshazi, K., Ortmann, O., Halmos, G., Hohla, F., & Buchholz, S. (2009). Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog, AN-162 (AEZS-124), and its effects on tumor growth inhibition. Anti-cancer drugs, 20(7), 553-558. https://doi.org/10.1097/CAD.0b013e32832d190b