IMR Press / FBE / Volume 3 / Issue 1 / DOI: 10.2741/E239

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
DNA methyltransferase inhibitor CDA-2 synergizes with high-dose thiotepa and paclitaxel in killing breast cancer stem cells
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1 Department of Medical Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), Peking University School of Oncology, Beijing Cancer Hospital and Institute, China

*Author to whom correspondence should be addressed.

Academic Editors: Wen G Jiang, Richard Ablin

Front. Biosci. (Elite Ed) 2011, 3(1), 240–249; https://doi.org/10.2741/E239
Published: 1 January 2011
(This article belongs to the Special Issue Bone metastasis, the molecular, cellular and clinical prospects)
Abstract

It has been suggested that breast cancer stem cells (CSCs), which characterized by CD44+CD24-/low, may result in treatment failure in patients with breast cancer. It is possible therefore that that inhibiting such subpopulation might subsequently improve clinical outcome. In the present study, we found that the CD44+CD24-/low CSCs, isolated from both human breast cell line MCF-7 and MDA-MB-231, were more resistant to thiotepa, paclitaxel and anthracycline, when compared with the non-breast cancer stem cell subset from the same cell lines, whereas the chemosensitivities were remarkably reversed by higher concentration of thiotepa and paclitaxel except for adriamycin. The percentage of CSCs was significantly decreased with an addition of DNA methyltransferase inhibitor CDA-2 and the expression of Smo, Shh, and Gli-1 of Hedgehog signaling pathway in CSCs was decreased. Of important findings, combination of thiotepa or paclitaxel with CDA-2 could significantly inhibit the proliferation of CSCs regardless of their dosages. These results unveiled that the selection of cytotoxic agents and increasing their dosage might be of great importance in the respect of eliminating CSCs. DNA methyltransferase inhibitor CDA-2 exhibited a synergistic effect with cytotoxic drugs, which might provide a conceptually new therapeutic strategy.

Keywords
Breast Cancer Stem Cells
Cytotoxic Drug
Hedgehog Signaling Pathway
High-dose Chemotherapy
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