Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells

Florian Hohla; Stefan Buchholz; Andrew V Schally; Awtar Krishan; Ferenc G Rick; Luca Szalontay; Andrea Papadia; Gabor Halmos; Frank Koster; Elmar Aigner; Christian Datz; Stephan Seitz

doi:10.1016/j.canlet.2010.01.018

Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells

Cancer Lett. 2010 Aug 1;294(1):35-42. doi: 10.1016/j.canlet.2010.01.018. Epub 2010 Feb 13.

Authors

Florian Hohla¹, Stefan Buchholz, Andrew V Schally, Awtar Krishan, Ferenc G Rick, Luca Szalontay, Andrea Papadia, Gabor Halmos, Frank Koster, Elmar Aigner, Christian Datz, Stephan Seitz

Affiliation

¹ Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Paracelsusstrasse 37, Oberndorf, Austria.

PMID: 20156671
DOI: 10.1016/j.canlet.2010.01.018

Abstract

The effect of the targeted cytotoxic somatostatin (SST) analog AN-162, consisting of doxorubicin (DOX) conjugated to SST carrier RC-121, was investigated on the growth of human colorectal cancer (CRC) cell lines HT-29, HCT-15, and HCT-116 and a DOX-resistant mouse leukemia cell line P388/R84. mRNA for SST-receptors and high affinity binding sites for SST were detected in all CRC cell lines and in P388/R84 cells. In contrast to DOX alone, AN-162 blocked HCT-116 cells and P388/R84 cells in S/G2 phase and increased the number of apoptotic cells. In vivo, AN-162 reduced the volume of CRC xenografts more effectively than its unconjugated components. Our results suggest that AN-162 inhibits growth of experimental CRC more effectively than DOX and increases sensitivity of DOX resistant human leukemia cells.

MeSH terms

2-Hydroxyphenethylamine / analogs & derivatives*
2-Hydroxyphenethylamine / therapeutic use
Aniline Compounds / therapeutic use*
Animals
Cell Cycle / drug effects
Cell Division
Cell Survival / drug effects
Colonic Neoplasms / genetics
Colonic Neoplasms / pathology*
Colorectal Neoplasms / epidemiology
Colorectal Neoplasms / mortality
Doxorubicin / therapeutic use*
Drug Resistance, Neoplasm*
Female
Humans
Leukemia, Experimental / drug therapy
Male
Mice
Mice, Nude
RNA, Messenger / genetics
Receptors, Somatostatin / genetics
Reverse Transcriptase Polymerase Chain Reaction
Somatostatin / analogs & derivatives*
Somatostatin / therapeutic use*

Substances

Aniline Compounds
RNA, Messenger
Receptors, Somatostatin
somatostatin receptor subtype-4
somatostatin receptor type 1
N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline
Somatostatin
2-Hydroxyphenethylamine
Doxorubicin
somatostatin receptor 5