Cancer Letters
Volume 295, Issue 1 , Pages 85-91, 1 September 2010

Histone deacetylase inhibitor FR235222 sensitizes human prostate adenocarcinoma cells to apoptosis through up-regulation of Annexin A1

  • Cosimo Walter D’Acunto

      Affiliations

    • Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Salerno, Italy
    • ,
  • Bianca Fontanella

      Affiliations

    • Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Salerno, Italy
    • ,
  • Manuela Rodriquez

      Affiliations

    • Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Salerno, Italy
    • ,
  • Maurizio Taddei

      Affiliations

    • Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Siena, Italy
    • ,
  • Luca Parente

      Affiliations

    • Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Salerno, Italy
    • ,
  • Antonello Petrella

      Affiliations

    • Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Salerno, Italy
    • Corresponding Author InformationCorresponding author. Address: Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy. Tel.: +39 089 969762; fax: +39 089 969602.

Received 12 January 2010; received in revised form 17 February 2010; accepted 19 February 2010. published online 15 March 2010.

Abstract 

The reduction of Annexin A1 (ANXA1) expression, commonly associated with prostate cancer, could be due to elevated activity of histone deacetylases. We have investigated the mechanisms of apoptotic effects of FR235222 in LNCaP cell line and the role of ANXA1. We showed that treatment with FR235222 induced apoptosis through a caspase-dependent mechanism. FR235222 was able to increase the protein levels of ANXA1 at a transcriptional level. Finally, the inhibition of ANXA1 expression by siRNA leads to a partial reduction of FR235222-induced apoptosis. The results suggest that elevated activity of HDACs is responsible for the reduction of ANXA1, indicating that ANXA1 expression is a contributing factor to the proapoptotic effects in prostate cancer.

Keywords: Annexin A1, Histone deacetylase inhibitors, Apoptosis, Prostate cancer

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PII: S0304-3835(10)00117-5

doi:10.1016/j.canlet.2010.02.016

Cancer Letters
Volume 295, Issue 1 , Pages 85-91, 1 September 2010

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