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

J Formos Med Assoc. 2017 Jan;116(1):41-48. doi: 10.1016/j.jfma.2016.01.004. Epub 2016 Feb 12.

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.

Keywords: cancer stemness; oral squamous cell carcinomas; sulforaphane.

MeSH terms

  • Aldehyde Dehydrogenase 1 Family
  • Animals
  • Anticarcinogenic Agents / administration & dosage*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dietary Supplements
  • Disease Models, Animal
  • Humans
  • Hyaluronan Receptors / metabolism
  • Isoenzymes / metabolism
  • Isothiocyanates / administration & dosage*
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects*
  • Retinal Dehydrogenase / metabolism
  • Sulfoxides

Substances

  • Anticarcinogenic Agents
  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • Isoenzymes
  • Isothiocyanates
  • MicroRNAs
  • Mirn200 microRNA, mouse
  • Sulfoxides
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase
  • sulforaphane