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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2014

01-02-2014 | Preclinical study

A combination treatment with DNA methyltransferase inhibitors and suramin decreases invasiveness of breast cancer cells

Authors: Sahra Borges, Heike R. Döppler, Peter Storz

Published in: Breast Cancer Research and Treatment | Issue 1/2014

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Abstract

The treatment of patients with invasive breast cancer remains a major issue because of the acquisition of drug resistance to conventional chemotherapy. Here we propose a new therapeutic strategy by combining DNA methyltransferase inhibitors (DMTIs) with suramin. Cytotoxic effects of suramin or combination treatment with DMTIs were determined in highly invasive breast cancer cell lines MDA-MB-231, BT-20 and HCC1954, or control cells. In addition, effects on cell invasion were determined in 3-dimensional cell culture assays. DMTI-mediated upregulation of Protein Kinase D1 (PKD1) expression was shown by Western blotting. Effects of suramin on PKD1 activity was determined in vitro and in cells. The importance of PKD1 in mediating the effects of such combination treatment in cell invasion was demonstrated using 3D cell culture assays. A proof of principal animal experiment was performed showing that PKD1 is critical for breast cancer growth. We show that when used in combination, suramin and DMTIs impair the invasive phenotype of breast cancer cells. We show that PKD1, a kinase that previously has been described as a suppressor of tumor cell invasion, is an interface for both FDA-approved drugs, since the additive effects observed are due to DMTI-mediated re-expression and suramin-induced activation of PKD1. Our data reveal a mechanism of how a combination treatment with non-toxic doses of suramin and DMTIs may be of therapeutic benefit for patients with aggressive, multi-drug resistant breast cancer.
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Metadata
Title
A combination treatment with DNA methyltransferase inhibitors and suramin decreases invasiveness of breast cancer cells
Authors
Sahra Borges
Heike R. Döppler
Peter Storz
Publication date
01-02-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2857-2

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