A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC

Leleesha Samaraweera, Alfred Adomako, Alicia Rodriguez-Gabin, Hayley M. McDaid

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is interest in evaluating alternate dosing schedules and novel combinations of pano for the treatment of upper aerodigestive and lung malignancies; thus we evaluated it in combination with Taxol, a chemotherapeutic with activity in both diseases. Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to senescence rather than potentiation of cell death. Senescence occurred following cisplatin- or Taxol-treatment in cell lines from both cancer types and was associated with decreased histone 3 (H3) acetylation and increased Bcl-xL expression: the latter a biomarker of senescence and target of anti-senescence therapeutics, or senolytics. Since H3 acetylation and Bcl-xL expression were altered in senescence, we subsequently evaluated pano as a senolytic in chemotherapy-treated cancer cells enriched for senescent cells. Pano caused cell death at significantly higher rates compared to repeat dosing with chemotherapy. This was associated with decreased expression of Bcl-xL and increased acetylated H3, reversing the expression patterns observed in senescence. These data support evaluating pano as a post-chemotherapy senolytic with the potential to kill persistent senescent cells that accumulate during standard chemotherapy in NSCLC and HNSCC.

Original languageEnglish (US)
Article number1900
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Head and Neck Neoplasms
Non-Small Cell Lung Carcinoma
Pharmaceutical Preparations
Histones
Drug Therapy
Acetylation
Paclitaxel
Cell Death
Cell Line
Neoplasms
Histone Deacetylase Inhibitors
Cisplatin
Carcinoma, squamous cell of head and neck
panobinostat
Appointments and Schedules
Therapeutics
Biomarkers
Lung

ASJC Scopus subject areas

  • General

Cite this

A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC. / Samaraweera, Leleesha; Adomako, Alfred; Rodriguez-Gabin, Alicia; McDaid, Hayley M.

In: Scientific Reports, Vol. 7, No. 1, 1900, 01.12.2017.

Research output: Contribution to journalArticle

Samaraweera, Leleesha ; Adomako, Alfred ; Rodriguez-Gabin, Alicia ; McDaid, Hayley M. / A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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