The histone deacetylase inhibitor LBH589 enhances the anti-myeloma effects of chemotherapy in vitro and in vivo.
Panobinostat (LBH589) is a potent histone deacetylase inhibitor (HDACi) that has shown anti-tumor activity in preclinical studies in both solid and hematological malignancies. We evaluated the anti-multiple myeloma (MM) effects of LBH589 alone and with melphalan or doxorubicin using MM cell lines and our human MM xenograft model LAGλ-1. LBH589 treatment resulted in increased acetylation of histones, induction of caspase cleavage, inhibition of cell proliferation and synergistic anti-MM effects with melphalan or doxorubicin in vitro. LBH589 with melphalan or doxorubicin also showed significantly enhanced anti-myeloma activity in vivo. These findings provide the basis for clinical development of these combination therapies.
Sanchez
Eric
E
Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA.
Shen
Jing
J
Steinberg
Jeffrey
J
Li
Mingjie
M
Wang
Cathy
C
Bonavida
Benjamin
B
Chen
Haiming
H
Li
Zhi-Wei
ZW
Berenson
James R
JR
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D007211:Indoles; D008558:Melphalan / Q000008:administration & dosage; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D000077767:Panobinostat
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007074:Immunoglobulin G; D007211:Indoles; D004317:Doxorubicin; D000077767:Panobinostat; D020169:Caspases; D008558:Melphalan