Chia-Ming Liu1, Chih-Yu Peng1, Yi-Wen Liao2, Ming-Yi Lu1, Meng-Lun Tsai2, Jung-Chun Yeh1, Chuan-Hang Yu3, Cheng-Chia Yu4. 1. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. 2. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan. 3. 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. 4. 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.
Abstract
BACKGROUND/ PURPOSE: 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. CONCLUSION: 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.
BACKGROUND/ PURPOSE: 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. CONCLUSION: 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: Osama A Elkashty; Ramy Ashry; Ghada Abu Elghanam; Hieu M Pham; Xinyun Su; Camille Stegen; Simon D Tran Journal: Med Oncol Date: 2018-08-04 Impact factor: 3.064