title: Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) are deemed as the driving force of tumorigenesis in oral squamous cell carcinomas (OSCCs). In this study, we investigated the chemotherapeutic effect of sulforaphane, a dietary component from broccoli sprouts, on targeting OSCC-CSCs.
  
  
  METHODS
  The effect of sulforaphane on normal oral epithelial cells (SG) and sphere-forming OSCC-CSCs isolated from SAS and GNM cells was examined. ALDH1 activity and CD44 positivity of OSCC-CSCs with sulforaphane treatment was assessed by flow cytometry analysis. In vitro and in vivo tumorigenicity assays of OSCC-CSCs with sulforaphane treatment were presented.
  
  
  RESULTS
  We observed that the sulforaphane dose-dependently eliminated the proliferation rate of OSCC-CSCs, whereas the inhibition on SG cells proliferation was limited. Cancer stemness properties including self-renewal, CD44 positivity, and ALDH1 activity were also decreased in OSCC-CSCs with different doses of sulforaphane treatment. Moreover, sulforaphane treatment of OSCC-CSCs decreased the migration, invasion, clonogenicity, and in vivo tumorigenicity of xenograghts. Sulforaphane treatment resulted in a dose-dependent increase in the levels of tumor suppressive miR200c.
  
  
  CONCLUSIONS
  These lines of evidence suggest that sulforaphane can suppress the cancer stemness and tumor-initiating properties in OSCC-CSCs both in vitro and in vivo.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Liu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Peng
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liao
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Lu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Meng-Lun
authors.initials: ML
authors.lastname: Tsai
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Yeh
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: tao2008@csmu.edu.tw.
authors.forename: Chuan-Hang
authors.initials: CH
authors.lastname: Yu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: ccyu@csmu.edu.tw.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D017879:Isothiocyanates; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D013454:Sulfoxides; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; C016766:sulforaphane
keywords: cancer stemness; oral squamous cell carcinomas; sulforaphane