Belinostat and Vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma.

Belinostat and Vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma. Cancer Biol Ther. 2016 Oct 28;:0 Authors: Havas AP, Rodrigues KB, Bhakta A, Demirjian JA, Hahn S, Tran J, Scavello M, Tula-Sanchez AA, Zeng Y, Schmelz M, Smith CL Abstract Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy that has a 60 percent five-year survival rate, highlighting a need for new therapeutic approaches. Histone deacetylase inhibitors (HDACi) are novel therapeutics being clinically-evaluated in combination with a variety of other drugs. However, rational selection of companion therapeutics for HDACi is difficult due to their poorly-understood, cell-type specific mechanisms of action. To address this, we developed a pre-clinical model system of sensitivity and resistance to the HDACi belinostat using DLBCL cell lines. In the current study, we demonstrate that cell lines sensitive to the cytotoxic effects of HDACi undergo early mitotic arrest prior to apoptosis. In contrast, HDACi-resistant cell lines complete mitosis after a short delay and arrest in G1. To force mitotic arrest in HDACi-resistant cell lines, we used low dose vincristine or paclitaxel in combination with belinostat and observed synergistic cytotoxicity. Belinostat curtails vincristine-induced mitotic arrest and triggers a strong apoptotic re...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research