MYB down-regulation enhances sensitivity of U937 myeloid leukemia cells to the histone deacetylase inhibitor LBH589 in vitro and in vivo

Ping Ye; Liang Zhao; Crystal McGirr; Thomas J Gonda

doi:10.1016/j.canlet.2013.09.022

MYB down-regulation enhances sensitivity of U937 myeloid leukemia cells to the histone deacetylase inhibitor LBH589 in vitro and in vivo

Cancer Lett. 2014 Feb 1;343(1):98-106. doi: 10.1016/j.canlet.2013.09.022. Epub 2013 Sep 26.

Authors

Ping Ye¹, Liang Zhao², Crystal McGirr¹, Thomas J Gonda³

Affiliations

¹ School of Pharmacy, The University of Queensland, Brisbane, Queensland 4102, Australia; The University of Queensland Diamantina Institute, Brisbane, Queensland 4102, Australia.
² Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
³ School of Pharmacy, The University of Queensland, Brisbane, Queensland 4102, Australia; The University of Queensland Diamantina Institute, Brisbane, Queensland 4102, Australia. Electronic address: t.gonda@uq.edu.au.

PMID: 24075958
DOI: 10.1016/j.canlet.2013.09.022

Abstract

The effect of combining MYB suppression with the histone deacetylase inhibitor LBH589 was studied in human myeloid leukemia cell lines. MYB knockdown inhibited proliferation and induced apoptosis in U937 and K562 cells in vitro, and also sensitized both to the pro-apoptotic effect of LBH589. This was accompanied by enhanced expression of the pro-apoptotic BCL2 family members BOK and BIM. U937 cells carrying inducible MYB shRNA were also transplanted into NOD/SCID mice. The combination of MYB knockdown and LBH589 prolonged survival compared to either treatment alone, suggesting that further development of such combinations might lead to effective and safe leukemia therapies.

Keywords: AML; Apoptosis; LBH589/Panobinostat; MYB; Xenograft.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Apoptosis
Cell Cycle
Cell Line, Tumor
Cell Survival
Gene Expression Regulation, Neoplastic*
Histone Deacetylase Inhibitors / pharmacology*
Humans
Hydroxamic Acids / pharmacology*
Indoles / pharmacology*
K562 Cells
Leukemia, Myeloid, Acute / pathology
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Transplantation
Panobinostat
Proto-Oncogene Proteins c-myb / metabolism*
RNA Interference
U937 Cells

Substances

Antineoplastic Agents
Histone Deacetylase Inhibitors
Hydroxamic Acids
Indoles
Proto-Oncogene Proteins c-myb
Panobinostat