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@ARTICLE{Klose:128912,
author = {J. Klose and J. Eissele and C. Volz and S. Schmitt$^*$ and
A. Ritter and S. Ying and T. Schmidt and U. Heger and M.
Schneider and A. Ulrich},
title = {{S}alinomycin inhibits metastatic colorectal cancer growth
and interferes with {W}nt/β-catenin signaling in {CD}133(+)
human colorectal cancer cells.},
journal = {BMC cancer},
volume = {16},
number = {1},
issn = {1471-2407},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2017-04925},
pages = {896},
year = {2016},
abstract = {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.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.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.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.},
keywords = {AC133 Antigen (NLM Chemicals) / PROM1 protein, human (NLM
Chemicals) / Pyrans (NLM Chemicals) / salinomycin (NLM
Chemicals)},
cin = {W220},
ddc = {610},
cid = {I:(DE-He78)W220-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27855654},
pmc = {pmc:PMC5114842},
doi = {10.1186/s12885-016-2879-8},
url = {https://inrepo02.dkfz.de/record/128912},
}