The histone deacetylase inhibitor LBH589 enhances the anti-myeloma effects of chemotherapy in vitro and in vivo

Leuk Res. 2011 Mar;35(3):373-9. doi: 10.1016/j.leukres.2010.06.026. Epub 2010 Jul 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage
  • Drug Synergism
  • Flow Cytometry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Immunoglobulin G / blood
  • In Vitro Techniques
  • Indoles
  • Melphalan / administration & dosage
  • Mice
  • Mice, SCID
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology*
  • Panobinostat


  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Immunoglobulin G
  • Indoles
  • Doxorubicin
  • Panobinostat
  • Caspases
  • Melphalan