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

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.

• Authors: Chi-Hao Wu, Bo-Han Hong, Chi-Tang Ho, Gow-Chin Yen
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 63 Issue 9 Pg. 2432-41 (Mar 11 2015) ISSN: 1520-5118 [Electronic] United States
• PMID: 25686711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Catechols
• Oncogene Protein p55(v-myc)
• Stilbenes
• Cyclin D1
• pterostilbene
• shogaol

Topics

• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Catechols (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin D1 (genetics, metabolism)
• Female
• Humans
• Neoplastic Stem Cells (cytology, drug effects, metabolism)
• Oncogene Protein p55(v-myc) (genetics, metabolism)
• Signal Transduction (drug effects)
• Stilbenes (pharmacology)