Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction

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• 作者：Chia-Ming Liu^a ; ^b ; ^d ; Chih-Yu Peng^a ; ^b ; ^d ; Yi-Wen Liao^a ; Ming-Yi Lu^a ; ^b ; Meng-Lun Tsai^a ; Jung-Chun Yeh^a ; ^b ; Chuan-Hang Yu^a ; ^b ; ^c ; ^{tao2008@csmu.edu.tw} ; Cheng-Chia Yu^a ; ^b ; ^c ; ^{ccyu@csmu.edu.tw}
• 关键词：cancer stemness ; oral squamous cell carcinomas ; sulforaphane
• 刊名：Journal of the Formosan Medical Association
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：116
• 期：1
• 页码：41-48
• 全文大小：1247 K
• 卷排序：116

文摘

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.MethodsThe 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.ResultsWe 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.ConclusionThese lines of evidence suggest that sulforaphane can suppress the cancer stemness and tumor-initiating properties in OSCC-CSCs both in vitro and in vivo.