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Open Access 01-12-2010 | Research article

Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype

Authors: Junichi Kurebayashi, Naoki Kanomata, Takuya Moriya, Yuji Kozuka, Mika Watanabe, Hiroshi Sonoo

Published in: BMC Cancer | Issue 1/2010

Abstract

Background

Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding and further investigate combined antitumor effects of dasatinib with cytotoxic agents, a panel of breast cancer cell lines of various subtypes was treated with dasatinib and/or chemotherapeutic agents.

Methods

Seven human breast cancer cell lines were treated with dasatinib and/or seven chemotherapeutic agents. Effects of the treatments on c-Src activation, cell growth, cell cycle, apoptosis and the proportion of aldehyde dehydrogenase (ALDH) 1-positive cells were examined.

Results

The 50%-growth inhibitory concentrations (IC₅₀s) of dasatinib were much lower in two basal B cell lines than those in the other cell lines. The IC₅₀s of chemotherapeutic agents were not substantially different among the cell lines. Dasatinib enhanced antitumor activity of etoposide in the basal B cell lines. Dasatinib induced a G1-S blockade with a slight apoptosis, and a combined treatment of dasatinib with etoposide also induced a G1-S blockade in the basal B cell lines. Dasatinib decreased the expression levels of phosphorylated Src in all cell lines. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in the basal B cell lines but not in the other cell lines.

Conclusions

The present study indicates that dasatinib preferentially inhibits the growth of breast cancer cells of the basal B subtype associated with a significant loss of putative cancer stem cell population. A combined use of dasatinib with etoposide additively inhibits their growth. Further studies targeting breast cancers of the basal B subtype using dasatinib with cytotoxic agents are warranted.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/568/prepub

Title: Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype
Authors: Junichi Kurebayashi
Naoki Kanomata
Takuya Moriya
Yuji Kozuka
Mika Watanabe
Hiroshi Sonoo
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-10-568

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