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


CONCLUSIONS
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.
Konstantinopoulos
Panagiotis A
PA
Department of Biological Chemistry, Medical School, University of Athens, Athens, and Department of Pathology, Aeghion General Hospital, Greece.
Vandoros
Gerasimos P
GP
Papavassiliou
Athanasios G
AG
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C087123:romidepsin; D006655:Histone Deacetylases