Gene targets of sulforaphane in head and neck squamous cell carcinoma

  • Authors:
    • Lanlin Hu
    • Hua Li
    • Eliot D. Lee
    • Jennifer R. Grandis
    • Julie E. Bauman
    • Daniel E. Johnson
  • View Affiliations

  • Published online on: October 23, 2019     https://doi.org/10.3892/mmr.2019.10766
  • Pages: 5335-5344
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Abstract

Patients who have undergone curative‑intent therapy for head and neck squamous cell carcinoma (HNSCC) exhibit a high rate of development of second primary tumors (SPTs), which are frequently lethal. A chemoprevention strategy that prevents SPTs would have a major impact on patient outcomes. Sulforaphane, a naturally‑occurring compound derived from cruciferous vegetables exhibits chemopreventive activity against HNSCC in a preclinical model. The effects of sulforaphane are considered to be mediated, in large part, through increased protein expression of the transcription factor nuclear factor erythroid 2‑related factor 2 (NRF2). Development of sulforaphane chemoprevention for HNSCC would benefit from the identification of robust biomarkers of sulforaphane activity in HNSCC cells and normal mucosal epithelial cells. The present study revealed that sulforaphane potently induces multiple oxidative stress‑associated genes at the RNA and protein levels, in HNSCC cells and Het‑1A cells, a non‑tumorigenic mucosal epithelial cell line. In the present analysis, HMOX1 and HSPA1A were identified as the most highly upregulated genes following sulforaphane treatment, suggesting their potential value as biomarkers to guide clinical trials. Sulforaphane induction of HMOX1 and HSPA1A was validated in vivo in murine tissues. Furthermore, the impact of sulforaphane treatment of HNSCC cells on the expression levels of natural killer group 2D (NKG2D) and DNAX accessory molecule‑1 (DNAM‑1) ligands, which are activators of natural killer (NK) cells, was examined. NRF2‑dependent upregulation of the NKG2D ligand MICA/B was observed. However, only one of the six HNSCC cell lines studied exhibited enhanced sensitivity to NK cell‑mediated killing following sulforaphane treatment, suggesting that this may not be a general mechanism of sulforaphane chemopreventive activity in HNSCC. In summary, the present study identified robust biomarkers of sulforaphane activity in HNSCC and normal tissues, supporting their application in the development of sulforaphane chemoprevention approaches for HNSCC.

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December 2019
Volume 20 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Hu, L., Li, H., Lee, E.D., Grandis, J.R., Bauman, J.E., & Johnson, D.E. (2019). Gene targets of sulforaphane in head and neck squamous cell carcinoma. Molecular Medicine Reports, 20, 5335-5344. https://doi.org/10.3892/mmr.2019.10766
MLA
Hu, L., Li, H., Lee, E. D., Grandis, J. R., Bauman, J. E., Johnson, D. E."Gene targets of sulforaphane in head and neck squamous cell carcinoma". Molecular Medicine Reports 20.6 (2019): 5335-5344.
Chicago
Hu, L., Li, H., Lee, E. D., Grandis, J. R., Bauman, J. E., Johnson, D. E."Gene targets of sulforaphane in head and neck squamous cell carcinoma". Molecular Medicine Reports 20, no. 6 (2019): 5335-5344. https://doi.org/10.3892/mmr.2019.10766