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J Agric Food Chem. 2015 Mar 11;63(9):2432-41. doi: 10.1021/acs.jafc.5b00002. Epub 2015 Feb 25.

Targeting cancer stem cells in breast cancer: potential anticancer properties of 6-shogaol and pterostilbene.

Author information

1
School of Nutrition and Health Sciences, Taipei Medical University , 250 Wu-Hsing Street, Taipei 110, Taiwan.

Abstract

Breast cancer stem cells (BCSCs) constitute a small fraction of the primary tumor that can self-renew and become a drug-resistant cell population, thus limiting the treatment effects of chemotherapeutic drugs. The present study evaluated the cytotoxic effects of five phytochemicals including 6-gingerol (6-G), 6-shogaol (6-S), 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-HF), nobiletin (NOL), and pterostilbene (PTE) on MCF-7 breast cancer cells and BCSCs. The results showed that 6-G, 6-S, and PTE selectively killed BCSCs and had high sensitivity for BCSCs isolated from MCF-7 cells that expressed the surface antigen CD44(+)/CD24(-). 6-S and PTE induced cell necrosis phenomena such as membrane injury and bleb formation in BCSCs and inhibited mammosphere formation. In addition, 6-S and PTE increased the sensitivity of isolated BCSCs to chemotherapeutic drugs and significantly increased the anticancer activity of paclitaxel. Analysis of the underlying mechanism showed that 6-S and PTE decreased the expression of the surface antigen CD44 on BCSCs and promoted β-catenin phosphorylation through the inhibition of hedgehog/Akt/GSK3β signaling, thus decreasing the protein expression of downstream c-Myc and cyclin D1 and reducing BCSC stemness.

KEYWORDS:

6-shogaol; breast cancer stem cells; hedgehog; mammospheres; pterostilbene

PMID:
25686711
DOI:
10.1021/acs.jafc.5b00002
[Indexed for MEDLINE]

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