The anti-histaminic cyproheptadine synergizes the antineoplastic activity of bortezomib in mantle cell lymphoma through its effects as a histone deacetylase inhibitor.
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.
Paoluzzi
Luca
L
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Scotto
Luigi
L
Marchi
Enrica
E
Seshan
Venkatraman E
VE
O'Connor
Owen A
OA
D000199:Actins / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D019938:Cyclin D1 / Q000378:metabolism; D003533:Cyproheptadine / Q000008:administration & dosage; D004195:Disease Models, Animal; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000008:administration & dosage
D000199:Actins; D001897:Boronic Acids; D006634:Histamine H1 Antagonists; D056572:Histone Deacetylase Inhibitors; D011480:Protease Inhibitors; D011719:Pyrazines; D019938:Cyclin D1; D003533:Cyproheptadine; D000069286:Bortezomib