Journal
CANCER LETTERS
Volume 417, Issue -, Pages 152-160Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.12.030
Keywords
Panobinostat; Histone deacetylase inhibitors; LBH589; Non-small cell lung cancer; Epigenetic therapy
Categories
Funding
- National Research Foundation Singapore
- Singapore Ministry of Education under their Research Centres of Excellence (RCE) Initiative
- Singapore Ministry of Health's National Medical Research Council (Senior Clinician Scientist Award) [NMRC/CSA/021/2010]
- NUHS Bridging Funds
- King Saud University [RG-1435-081]
Ask authors/readers for more resources
Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chemotherapy, suggesting a rational pairing of HDAC inhibitors with DNA damaging chemotherapeutic agents in the treatment of human malignancies. Here we report that panobinostat (LBH589), a potent pan-HDAC inhibitor, effectively curbed the proliferation of non-small cell lung cancer (NSCLC) cell lines A549, Calu-1, H226, H460, H838 and SKMES-1 at IC50 concentrations between 4 and 31 nmol/L via pleiotropic mechanisms, including crosstalk with EGFR signal transduction cascades. Combination therapy with carboplatin elicited rapid tumor cell kill and effectively restrained anchorage-independent clonogenic survival to a considerably greater extent over either monotherapy. The administration of carboplatin and panobinostat at clinically relevant doses to NOD-SCID xenograft mice drastically stalled disease progression by 92% as compared with negative control (P=.0026), which was greater than the 28% and 54% achieved with either carboplatin (P=.220) or panobinostat (P=.017) alone. These data demonstrate that panobinostat has strong anti-NSCLC activity and chemosensitizes tumors to carboplatin, thus justifying further evaluation of this combination approach in clinical trials. (C) 2018 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available