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Stem Cell Research and Therapy

, 4:146

First Online: 11 December 2013Received: 29 August 2013Revised: 28 October 2013Accepted: 03 December 2013

Abstract

IntroductionThe existence of breast cancer stem-like cells BCSCs has profound implications for cancer prevention. Genistein, a predominant isoflavone found in soy products, has multiple robust anti-tumor effects in various cancers, especially in the breast and prostate cancer. In this study, we aimed to evaluate genistein inhibition of BCSCs and its potential mechanism by culturing MCF-7 breast cancer cells and implanting these cells into nude mice.

MethodsCell counting, colony formation and cell apoptosis analysis were used to evaluate the effect of genistein on breast cancer cells’ growth, proliferation and apoptosis. We then used mammosphere formation assay and CD44CD24 staining to evaluate the effect of genistein on BCSCs in vitro. A nude mice xenograft model was employed to determine whether genistein could target BCSCs in vivo, as assessed by real-time polymerase chain reaction PCR and immunohistochemical staining. The potential mechanism was investigated utilizing real-time PCR, western blotting analysis and immunohistochemical staining.

ResultsGenistein inhibited the MCF-7 breast cancer cells’ growth and proliferation and promoted apoptosis. Both in vitro and in vivo genistein decreased breast cancer stem cells, and inhibited breast cancer stem-like cells through down-regulation of the Hedgehog-Gli1 Signaling Pathway.

ConclusionsWe demonstrated for the first time that genistein inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway. These findings provide support and rationale for investigating the clinical application of genistein in treating breast cancer, and specifically by targeting breast cancer stem cells.

AbbreviationsALDHaldehyde dehydrogenase

ALDH1aldehyde dehydrogenase isoform 1

BCSCbreast cancer stem-like cell

DMSOdimethyl sulfoxide

FITCfluorescein isothiocyanate

PtchPatched

ShhSonic hedgehog

SmoSmoothened.

Electronic supplementary materialThe online version of this article doi:10.1186-scrt357 contains supplementary material, which is available to authorized users.

Panhong Fan, Shujun Fan contributed equally to this work.

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