Document Detail


Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells.
MedLine Citation:
PMID:  20156671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Publication Detail:
Type:  Journal Article     Date:  2010-02-13
Journal Detail:
Title:  Cancer letters     Volume:  294     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Paracelsusstrasse 37, Oberndorf, Austria.
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MeSH Terms
Descriptor/Qualifier:
2-Hydroxyphenethylamine / analogs & derivatives*,  therapeutic use
Aniline Compounds / therapeutic use*
Animals
Cell Cycle / drug effects
Cell Division
Cell Survival / drug effects
Colonic Neoplasms / genetics,  pathology*
Colorectal Neoplasms / epidemiology,  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*,  therapeutic use*
Chemical
Reg. No./Substance:
0/Aniline Compounds; 0/RNA, Messenger; 0/Receptors, Somatostatin; 0/somatostatin receptor 5; 0/somatostatin receptor subtype-4; 0/somatostatin receptor type 1; 23214-92-8/Doxorubicin; 33189-65-0/N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline; 51110-01-1/Somatostatin; 7568-93-6/2-Hydroxyphenethylamine

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