title: Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line.
abstract: OBJECTIVE
  Cancer stem cells contribute to tumor recurrence, and a hypoxic environment is critical for maintaining cancer stem cells. Apigenin is a natural product with anticancer activity. However, the effect of apigenin on cancer stem cells remains unclear. Our aim was to investigate the effect of apigenin on cancer stem cell marker expression in head and neck squamous cell carcinoma cells under hypoxia.
  
  
  METHODS
  We used three head and neck squamous cell carcinoma cell lines; HN-8, HN-30, and HSC-3. The mRNA expression of cancer stem cell markers was determined by semiquantitative RT-PCR and Real-time PCR. The cytotoxic effect of apigenin was determined by MTT colorimetric assay. Flow cytometry was used to reveal the number of cells expressing cancer stem cell surface markers.
  
  
  RESULTS
  HN-30 cells, a cancer cell line from the pharynx, showed the greatest response to hypoxia by increasing their expression of CD44, CD105, NANOG, OCT-4, REX-1, and VEGF. Apigenin significantly decreased HN-30 cell viability in dose- and time-dependent manners. In addition, 40μM apigenin significantly down-regulated the mRNA expression of CD44, NANOG, and CD105. Consistent with these results, the hypoxia-induced increase in CD44+cells, CD105+cells, and STRO-1+cells was significantly abolished by apigenin.
  
  
  CONCLUSIONS
  Apigenin suppresses cancer stem cell marker expression and the number of cells expressing cell surface markers under hypoxia.
authors.affiliation: Interdepartmental Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yuwaporn
authors.initials: Y
authors.lastname: Ketkaew
authors.affiliation: Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Thanaphum
authors.initials: T
authors.lastname: Osathanon
authors.affiliation: Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Prasit
authors.initials: P
authors.lastname: Pavasant
authors.affiliation: Department of Pharmacology, Faculty of Dentistry, Chulalongkorn University, 34 Henri-Dunant Road, Pathumwan, Bangkok, 10330, Thailand. Electronic address: pl_sireerat@yahoo.com.
authors.forename: Sireerat
authors.initials: S
authors.lastname: Sooampon
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D000071063:Endoglin / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000187:drug effects / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000187:drug effects / Q000378:metabolism; D010614:Pharynx; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497483:CD44 protein, human; C064206:ENG protein, human; D000071063:Endoglin; D018960:Hyaluronan Receptors; D051741:Kruppel-Like Transcription Factors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C507976:ZFP42 protein, human; D047310:Apigenin
keywords: Apigenin; Cancer stem cells; Head and neck squamous cell carcinoma; Hypoxia