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Cancer Lett. 2017 May 28;394:52-64. doi: 10.1016/j.canlet.2017.02.023. Epub 2017 Feb 27.

Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells.

Author information

1
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
2
School of Science and Humanities, Husson University, Bangor, ME 04401, USA.
3
Department of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, ME 04401, USA.
4
Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
5
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: duxins@med.umich.edu.
6
Department of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, ME 04401, USA. Electronic address: zhangt@husson.edu.

Abstract

Triple negative breast cancer (TNBC) typically exhibits rapid progression, high mortality and faster relapse rates relative to other breast cancer subtypes. In this report we examine the combination of taxanes (paclitaxel or docetaxel) with a breast cancer stem cell (CSC)-targeting agent sulforaphane for use against TNBC. We demonstrate that paclitaxel or docetaxel treatment induces IL-6 secretion and results in expansion of CSCs in TNBC cell lines. Conversely, sulforaphane is capable of preferentially eliminating CSCs, by inhibiting NF-κB p65 subunit translocation, downregulating p52 and consequent downstream transcriptional activity. Sulforaphane also reverses taxane-induced aldehyde dehydrogenase-positive (ALDH+) cell enrichment, and dramatically reduces the size and number of primary and secondary mammospheres formed. In vivo in an advanced treatment orthotopic mouse xenograft model together with extreme limiting dilution analysis (ELDA), the combination of docetaxel and sulforaphane exhibits a greater reduction in primary tumor volume and significantly reduces secondary tumor formation relative to either treatment alone. These results suggest that treatment of TNBCs with cytotoxic chemotherapy would be greatly benefited by the addition of sulforaphane to prevent expansion of and eliminate breast CSCs.

KEYWORDS:

Cancer stem cell; Docetaxel; Paclitaxel; Sulforaphane; Triple negative breast cancer

PMID:
28254410
DOI:
10.1016/j.canlet.2017.02.023
[Indexed for MEDLINE]

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