Extracellular NAMPT/visfatin causes p53 deacetylation via NAD production and SIRT1 activation in breast cancer cells

Kiarash Behrouzfar, Mohammad Alaee, Mitra Nourbakhsh, Zafar Gholinejad, Abolfazl Golestani

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

Abstract

Visfatin, which is secreted as an adipokine and cytokine, has been implicated in cancer development and progression. In this study, we investigated the NAD-producing ability of visfatin and its relationship with SIRT1 (silent information regulator 2) and p53 to clarify the role of visfatin in breast cancer. MCF-7 breast cancer cells were cultured and treated with visfatin. SIRT1 activity was assessed by measuring fluorescence intensity from fluoro-substrate peptide. To investigate the effect of visfatin on p53 acetylation, SDS-PAGE followed by western blotting was performed using specific antibodies against p53 and its acetylated form. Total NAD was measured both in cell lysate and the extracellular medium by colorimetric method. Visfatin increased both extracellular and intracellular NAD concentrations. It also induced proliferation of breast cancer cells, an effect that was abolished by inhibition of its enzymatic activity. Visfatin significantly increased SIRT1 activity, accompanied by induction of p53 deacetylation. In conclusion, the results show that extracellular visfatin produces NAD that causes upregulation of SIRT1 activity and p53 deacetylation. These findings explain the relationship between visfatin and breast cancer progression.

Original languageEnglish
Pages (from-to)327-333
Number of pages7
JournalCell Biochemistry and Function
Volume35
Issue number6
DOIs
Publication statusPublished - Aug 2017
Externally publishedYes

Keywords

  • acetylation
  • breast cancer
  • p53
  • SIRT1
  • visfatin

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