A novel approach to eliminate therapy-resistant mantle cell lymphoma: synergistic effects of Vorinostat with Palbociclib

Nagendra K. Chaturvedi, Nathan D. Hatch, Garrett L. Sutton, Matthew Kling, Julie Marie Vose, Shantaram S Joshi

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Mantle cell lymphoma (MCL) represents an aggressive B-cell lymphoma with frequent relapse and poor survival. Recently, dysregulated histone-deacetylases (HDACs) and cell cycle CDK-Rb pathway have been shown to be commonly associated with MCL pathogenesis, and are considered promising targets for relapsed-lymphoma therapy. Therefore, we investigated the single agents and combination efficacy of HDACs inhibitor Vorinostat, CDK4/6 dual-inhibitor Palbociclib on MCL cell growth/survival and underlying molecular mechanism(s) using MCL cell lines including therapy-resistant MCL cell lines. Our results showed that both inhibitors as single agents or combined, significantly suppressed the cell growth and induced apoptosis in therapy-resistant and parental MCL lines. In addition, the combination of Vorinostat and Palbociclib significantly inhibited the activation of the key molecules of the CDK4/6-Rb pathway and HDAC activity and subsequently decreased the expression of Cyclin-D1 and Bcl-2. These studies demonstrated the potential for combining these two inhibitors as a novel therapeutic approach in refractory MCL therapy.

Original languageEnglish (US)
Pages (from-to)1214-1223
Number of pages10
JournalLeukemia and Lymphoma
Volume60
Issue number5
DOIs
StatePublished - Apr 16 2019

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Keywords

  • CDK4/CDK6 inhibitor
  • HDAC inhibitor
  • Mantle cell lymphoma
  • therapy-resistant MCL

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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