The anti-histaminic cyproheptadine synergizes the antineoplastic activity of bortezomib in mantle cell lymphoma through its effects as a histone deacetylase inhibitor

Luca Paoluzzi, Luigi Scotto, Enrica Marchi, Venkatraman E. Seshan, Owen A. O'Connor

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Cyproheptadine, an inhibitor of the H1 histamine receptors, has recently shown activity in models of leukaemia and myeloma, presumably through inhibition of cyclin-D expression. Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin-D1. We investigated the effect of cyproheptadine alone and in combination with the proteasome inhibitor bortezomib in models of MCL. The combination of these drugs was mathematically synergistic, producing significant reductions in the mitochondrial membrane potential leading to apoptosis. In a severe combined immunodeficient beige mouse model, cyproheptadine plus bortezomib demonstrated a statistically significant advantage compared to either agent alone.

Original languageEnglish (US)
Pages (from-to)656-659
Number of pages4
JournalBritish Journal of Haematology
Volume146
Issue number6
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Keywords

  • Bortezomib
  • Cyclin D1
  • Cyproheptadine
  • Hdac inhibitor
  • Mantle cell lymphoma

ASJC Scopus subject areas

  • Hematology

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