HDAC inhibitor Vorinostat and BET inhibitor Plx51107 epigenetic agents’ combined treatments exert a therapeutic approach upon acute myeloid leukemia cell model

Abstract

The process of cancer initiation and development is regulated via the transcriptional expression of cells going under genomic and epigenetic changes. Targeting epigenetic "readers", i.e. bromodomains (BRD) and post-translational modi cations of nucleosomal histone proteins regulate gene expression in both cancerous and healthy cells.In this study, the new epigenetic agent BRD inhibitor PLX51107 and histone deacetylase (HDAC) inhibitor SAHA' s (vorinostat) single/combined applications' re ections were analyzed in case of cell proliferation, cytotoxicity, apoptosis, cell cycle arrest, and nally target gene expression regulation upon both AML and healthy B-lymphocyte cells; HL60 and NCI-BL2171, respectively; in vitro.Since mono treatments of either Vorinostat or Plx51107 regulated cellular responses such as growth, proliferation, apoptosis, and cell cycle arrest of tumor cells; their combination treatments exerted accelerated results. We detected that combined treatment of Plx51107 and vorinostat strengthened effects detected upon leukemic cells for gaining more sensitization to the agents, decreasing cell proliferation, dramatically inducing apoptosis, and cell cycle arrest; thus regulating target gene expressions. We have shown for the rst time that the newly analyzed BRD inhibitor Plx51107 could be a promising therapeutic approach for hematological malignancies and its mono or combined usage might support a rapid transition to clinical trials.

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review)

“…In addition, the combination between BRD4 and other inhibitors should be considered. For example, BRD4 inhibitor in combination with suberoylanilide hydroxamic acid as a histone deacetylase inhibitor have been tested and exhibited promising results in certain tumors ( 158 , 159 ). This approach could further expand therapeutic options but may also need to proceed with caution due to adverse effects of such inhibitions.…”