The inhibitory and transcriptional effects of the epigenetic repurposed drugs hydralazine and valproate in lymphoma cells.

ABSTRACT

Lymphoma is a disease that affects countless lives each year. In order to combat this disease, researchers have been exploring the potential of DNMTi and HDACi drugs. These drugs target the cellular processes that contribute to lymphomagenesis and treatment resistance. Our research evaluated the effectiveness of a combination of two such drugs, hydralazine (DNMTi) and valproate (HDACi), in B-cell and T-cell lymphoma cell lines. Here we show that the combination of hydralazine and valproate decreased the viability of cells over time, leading to the arrest of cell-cycle and apoptosis in both B and T-cells. This combination of drugs proved to be synergistic, with each drug showing significant growth inhibition individually. Microarray analyses of HuT 78 and Raji cells showed that the combination of hydralazine and valproate resulted in the up-regulation of 562 and 850 genes, respectively, while down-regulating 152 and 650 genes. Several proapoptotic and cell cycle-related genes were found to be up-regulated. Notably, three and five of the ten most up-regulated genes in HuT 78 and Raji cells, respectively, were related to immune function. In summary, our study suggests that the combination of hydralazine and valproate is an effective treatment option for both B- and T-lymphomas. These findings are highly encouraging, and we urge further clinical evaluation to validate our research and potentially improve lymphoma treatment.