title: The histone deacetylase inhibitor LBH589 enhances the anti-myeloma effects of chemotherapy in vitro and in vivo.
abstract: 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.
authors.affiliation: Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Sanchez
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Steinberg
authors.forename: Mingjie
authors.initials: M
authors.lastname: Li
authors.forename: Cathy
authors.initials: C
authors.lastname: Wang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonavida
authors.forename: Haiming
authors.initials: H
authors.lastname: Chen
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Li
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
mesh_terms: 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
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007074:Immunoglobulin G; D007211:Indoles; D004317:Doxorubicin; D000077767:Panobinostat; D020169:Caspases; D008558:Melphalan