Tumor Biology

, Volume 31, Issue 6, pp 659–666 | Cite as

A combination treatment with SAHA and ad-p63/p73 shows an enhanced anticancer effect in HNSCC

  • Seon-Hui Shim
  • Choon-Taek Lee
  • Jae-Jung Lee
  • So-Yeon Kim
  • J. Hun Hah
  • Dae Seog Heo
  • Myung-Whun Sung
Research Article

Abstract

Suberoylanilide hydroxamic acid (SAHA) is one of the most widely used histone deacetylase inhibitors. However, the potential advantage of SAHA has not been sufficiently validated as an adjunct to gene therapy of head and neck squamous cell carcinoma (HNSCC). SAHA has been shown to boost the efficiency of gene transfer by upregulating the expression of coxsackie adenoviral receptor on treated cells. The p53 family genes, p63 and p73, have been shown to have characteristics similar to p53, and although they are not confirmed as tumor suppressors, DNA-damaging signals induce their overexpression. We previously reported that the adenovirus-mediated transfer of p63 or p73 showed an effective cancer-killing effect similar to that of p53. In this study, we combined SAHA with adenoviral delivery of p63 or p73 to enhance the efficiency of gene therapy. This combination resulted in a significantly enhanced cancer-killing effect in HNSCC cell lines but had no effect on normal human fibroblasts. SAHA treatment added to ad-p63/p73 gene delivery caused an increase in p21 expression and cleaved poly-ADP ribose polymerase. Our results indicate that adjuvant SAHA treatment could be developed as a therapeutic strategy to enhance the efficiency of adenoviral gene transfer in the treatment of cancer.

Keywords

Combination gene therapy p63 p73 SAHA HNSCC 

Notes

Acknowledgements

This study was supported by Korea Science and Engineering Foundation grants 2005-01159(M-W Sung), 2008-00728(C-T Lee), and 314-2007-1-E00114 (M-W Sung).

Disclosure Statement

The authors declare that they have no conflict of interest.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Seon-Hui Shim
    • 1
    • 2
  • Choon-Taek Lee
    • 4
    • 5
  • Jae-Jung Lee
    • 1
    • 2
  • So-Yeon Kim
    • 1
    • 2
  • J. Hun Hah
    • 3
  • Dae Seog Heo
    • 1
    • 2
    • 6
    • 7
  • Myung-Whun Sung
    • 1
    • 2
    • 3
    • 7
    • 8
  1. 1.Department of Molecular Tumor BiologyCollege of Medicine, Seoul National UniversitySeoulSouth Korea
  2. 2.Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  3. 3.Department of OtorhinolaryngologySeoul National University College of MedicineSeoulSouth Korea
  4. 4.Division of Pulmonary and Care Medicine, Department of Internal MedicineLung Institute of Medical Research CenterSeongnamSouth Korea
  5. 5.Department of Medicine and Respiratory CenterSeoul National University Bundang HospitalSeongnamSouth Korea
  6. 6.Department of Internal MedicineSeoul National University HospitalSeoulSouth Korea
  7. 7.Sensory Organ Research InstituteSeoul National University Medical Research CenterSeoulSouth Korea
  8. 8.Clinical Research InstituteSeoul National University HospitalSeoulSouth Korea

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