Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 63, Issue 9, Pages 2432-2441Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.5b00002
Keywords
breast cancer stem cells; hedgehog; mammospheres; pterostilbene; 6-shogaol
Funding
- Ministry of Science and Technology, Taiwan [MOST99-2628-B005-002-MY3]
- Ministry of Education, Taiwan, under the ATU plan
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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 beta-catenin phosphorylation through the inhibition of hedgehog/Akt/GSK3 beta signaling, thus decreasing the protein expression of downstream c-Myc and cyclin D1 and reducing BCSC stemness.
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