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Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
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Published on: February 27, 2016

Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer

Turki Y Alhazzazi1, Pachiyappan Kamarajan, Nam Joo

  • 1Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, USA.

Cancer
|April 8, 2011
PubMed
Abstract

Insights

Sirtuin 3 (SIRT3) is overexpressed in oral squamous cell carcinoma (OSCC), promoting cancer cell growth. Reducing SIRT3 inhibits OSCC proliferation and increases sensitivity to treatments, identifying SIRT3 as a potential therapeutic target for oral cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Sirtuins (SIRT1-7) are NAD-dependent deacetylases involved in carcinogenesis.
  • The specific role of sirtuins in oral cancer remains largely uninvestigated.

Purpose of the Study:

  • To investigate the role of sirtuins in oral cancer carcinogenesis.
  • To determine if sirtuins are potential therapeutic targets for oral cancer.

Main Methods:

  • Compared sirtuin expression in oral squamous cell carcinoma (OSCC) cell lines and normal oral keratinocytes.
  • Utilized tissue microarrays to assess clinical relevance of SIRT3 overexpression.
  • Investigated SIRT3's role in OSCC proliferation, survival, and sensitivity to radiation and cisplatin.
  • Evaluated SIRT3's in vivo effect on OSCC tumor growth in a murine model.

Main Results:

  • SIRT3 was found to be significantly overexpressed in OSCC cell lines and tumors compared to other sirtuins.
  • Down-regulation of SIRT3 inhibited OSCC cell proliferation and survival in vitro.
  • SIRT3 inhibition enhanced OSCC sensitivity to ionizing radiation and cisplatin treatments.
  • Reduced SIRT3 expression led to decreased OSCC tumor burden in vivo.

Conclusions:

  • SIRT3 acts as a promoter in oral cancer carcinogenesis by enhancing cell proliferation and survival.
  • SIRT3 represents a novel and potential therapeutic target for the treatment of oral cancer.

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