5-Azacytidine Induces Anoikis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells

Molecules

Hsueh-Wei Chang⁴  Hui-Chun Wang³  Chiau-Yi Chen³  Ting-Wei Hung³  Ming-Feng Hou¹  Shyng-Shiou F. Yuan⁵  Chih-Jen Huang² 

[1] Cancer Center and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; E-Mail:;Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan;Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; E-Mails:;Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; E-Mail:;Translational Research Center, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; E-Mail:

关键词: cancer stem cell;    breast cancer;    anoikis;   

DOI  :  10.3390/molecules19033149

来源: mdpi

【 摘 要 】

Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC₅₀ of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.