eprintid: 22186
rev_number: 12
eprint_status: archive
userid: 1589
dir: disk0/00/02/21/86
datestamp: 2016-11-22 13:30:21
lastmod: 2024-05-04 01:45:44
status_changed: 2016-11-22 13:30:21
type: article
metadata_visibility: show
creators_name: Klose, Johannes
creators_name: Eissele, Jana
creators_name: Volz, Claudia
creators_name: Schmitt, Steffen
creators_name: Ritter, Alina
creators_name: Ying, Shen
creators_name: Schmidt, Thomas
creators_name: Heger, Ulrike
creators_name: Schneider, Martin
creators_name: Ulrich, Alexis
title: Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells
subjects: ddc-610
divisions: i-850300
divisions: i-910200
abstract: Background: The polyether antibiotic Salinomycin (Sal) is regarded as an inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer (CRC) cells in vitro has been demonstrated before. The aim of this study was to establish a murine model to investigate the effectiveness of Sal in vivo. Furthermore, we investigated the impact of Sal on Wnt/β-catenin signaling in human CD133+ CRC cells.   Methods: The two murine CRC cell lines MC38 and CT26 were used to analyze the impact of Sal on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro. For in vivo studies, CT26 cells were injected into syngeneic BALB/c mice to initiate (i) subcutaneous, (ii) orthotopic, or (iii) metastatic CRC growth. Sal was administered daily, 5-Fluoruracil served as a control. For mechanistic studies, the CD133+and CD133- subpopulations of human CRC cells were separated by flow cytometry and separately exposed to increasing concentrations of Sal. The impact on Wnt/β-catenin signaling was determined by Western blotting and quantitative PCR.   Results: Sal markedly impaired tumor cell viability, proliferation and migration, and induced necrotic cell death in vitro. CRC growth in vivo was likewise inhibited upon Sal treatment. Interference with Wnt signaling and reduced expression of the Wnt target genes Fibronectin and Lgr5 indicates a novel molecular mechanism, mediating anti-tumoral effects of Sal in CRC.   Conclusion: Sal effectively impairs CRC growth in vivo. Furthermore, Sal acts as an inhibitor of Wnt/β-catenin signaling. Thus, Salinomycin represents a promising candidate for clinical CRC treatment.
date: 2016
publisher: BioMed Central; Springer
id_scheme: DOI
ppn_swb: 1654398055
own_urn: urn:nbn:de:bsz:16-heidok-221869
language: eng
bibsort: KLOSEJOHANSALINOMYCI2016
full_text_status: public
publication: BMC Cancer
volume: 16
number: 896
place_of_pub: London; Berlin; Heidelberg
pagerange: 1-15
issn: 1471-2407
citation:   Klose, Johannes ; Eissele, Jana ; Volz, Claudia ; Schmitt, Steffen ; Ritter, Alina ; Ying, Shen ; Schmidt, Thomas ; Heger, Ulrike ; Schneider, Martin ; Ulrich, Alexis  (2016) Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells.  BMC Cancer, 16 (896).  pp. 1-15.  ISSN 1471-2407     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/22186/1/12885_2016_Article_2879.pdf