title: 5-azacytidine induces anoikis, inhibits mammosphere formation and reduces metalloproteinase 9 activity in MCF-7 human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. changhw@kmu.edu.tw.
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. wanghc@kmu.edu.tw.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. ionemicky@hotmail.com.
authors.forename: Chiau-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. kva916@yahoo.com.tw.
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Hung
authors.affiliation: Cancer Center and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. mifeho@kmu.edu.tw.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.affiliation: Translational Research Center, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. 1020005@kmuh.org.tw.
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. ccjjhh@kmu.edu.tw.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: Department of Biomedical Science and Environmental Biology, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. cntseng@kmu.edu.tw.
authors.forename: Chao-Neng
authors.initials: CN
authors.lastname: Tseng
mesh_terms: D023102:Anoikis / Q000187:drug effects; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D020780:Matrix Metalloproteinase 9; D001374:Azacitidine