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FK228 (depsipeptide): a HDAC inhibitor with pleiotropic antitumor activities

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Abstract

Purpose: The fundamental role of epigenetic events in carcinogenesis has resulted in the evolution of epigenetic targeting as a new paradigm in anticancer therapeutics. Aberrant histone deacetylase (HDAC) activity has been documented in many human malignancies resulting in the repression of tumor suppressor genes and promotion of tumorigenesis. FK228, also known as depsipeptide, is a novel, natural, bicyclic tetrapeptide with significant antitumor properties which are mostly mediated by inhibition of HDACs. Results: FK228 induces the expression of genes linked to the inhibition of cell growth, induction of cell differentiation, promotion of apoptotic cell death and inhibition of angiogenesis. Conclusion: Its multitargeting properties, its ability to act on non-histone targets, its clinical activity and its acceptable side-effect profile render FK228 a very promising novel anticancer agent.

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Authors and Affiliations

  1. Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece

    Panagiotis A. Konstantinopoulos & Athanasios G. Papavassiliou

  2. Department of Medicine, Division of Hematology–Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    Panagiotis A. Konstantinopoulos

  3. Department of Pathology, Aeghion General Hospital, 25100, Aeghion, Greece

    Gerasimos P. Vandoros

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  1. Panagiotis A. Konstantinopoulos
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  2. Gerasimos P. Vandoros
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  3. Athanasios G. Papavassiliou
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Correspondence to Athanasios G. Papavassiliou.

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Konstantinopoulos, P.A., Vandoros, G.P. & Papavassiliou, A.G. FK228 (depsipeptide): a HDAC inhibitor with pleiotropic antitumor activities. Cancer Chemother Pharmacol 58, 711–715 (2006). https://doi.org/10.1007/s00280-005-0182-5

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  • DOI: https://doi.org/10.1007/s00280-005-0182-5

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