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The anti‐histaminic cyproheptadine synergizes the antineoplastic activity of bortezomib in mantle cell lymphoma through its effects as a histone deacetylase inhibitor
Author(s) -
Paoluzzi Luca,
Scotto Luigi,
Marchi Enrica,
Seshan Venkatraman E.,
O’Connor Owen A.
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07797.x
Subject(s) - bortezomib , mantle cell lymphoma , cyproheptadine , cancer research , cyclin d1 , multiple myeloma , pharmacology , proteasome inhibitor , lymphoma , apoptosis , chemistry , medicine , cell cycle , receptor , biochemistry , serotonin
Summary 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.