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Improving Therapy for Refractory Mantle Cell Lymphoma Using Small Molecule Inhibitors Vorinostat and Palbociclib to Target Histone Deacetylase and Cyclin Dependent Kinase 4/6
Author(s) -
Hatch Nathan,
Chaturvedi Nagendra,
Kling Mathew,
Joshi Shantaram
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb118
Subject(s) - vorinostat , cancer research , palbociclib , romidepsin , histone deacetylase , lymphoma , mantle cell lymphoma , chemistry , medicine , histone , cancer , biochemistry , metastatic breast cancer , breast cancer , gene
Mantle Cell Lymphoma is a B‐Cell non‐Hodgkin lymphoma that accounts for 10% of all non‐Hodgkin lymphoma cases. It is extremely aggressive with a median survival time of approximately 5 years. There is a high rate of relapse due to therapy‐resistant tumor cells. There is currently no cure for refractory MCL. Here we demonstrate that using the histone deacetylase (HDAC) inhibitor, Vorinostat, in conjunction with cyclin dependent kinase (CDK) 4/6 inhibitor, Palbociclib, can be an effective method of treatment. This is shown using multiple in vitro experiments including: MTT assay, Annexin‐V staining, and colony formation assay. This combination of small molecule inhibitors has been found to decrease tumor cell proliferation by at least 25% as well as increase the rate of tumor cell apoptosis by at least 60% when compared to the use of these drugs on their own at equivalent concentrations. Future research will consist of in vivo studies using murine models. Support or Funding Information This publication was made possible by grants from the Lymphoma Research Foundation New York, NY, the State of Nebraska LB506 Funds, and the National Institute for General Medical Science (NIGMS) (8P20GM103427), a component of the National Institutes of Health (NIH) and its contents are the sole responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.