Histone deacetylase (HDAC) inhibitor has been a promising therapeutic option in cancer therapy due to its ability to induce growth arrest, differentiation, and apoptosis. In this study, we demonstrated that MPT0E028, a novel HDAC inhibitor, reduces the viability of B-cell lymphomas by inducing apoptosis and shows a more potent HDAC inhibitory effect compared to SAHA, the first HDAC inhibitor approved by the FDA. In addition to HDACs inhibition, MPT0E028 also possesses potent direct Akt targeting ability as measured by the kinome diversity screening assay. Also, MPT0E028 reduces Akt phosphorylation in B-cell lymphoma with an IC50 value lower than SAHA. Transient transfection assay revealed that both targeting HDACs and Akt contribute to the apoptosis induced by MPT0E028, with both mechanisms functioning independently. Microarray analysis also shows that MPT0E028 may regulate many oncogenes expression (e.g., TP53, MYC, STAT family). Furthermore, in vivo animal model experiments demonstrated that MPT0E028 (50-200 mg/kg, po, qd) prolongs the survival rate of mice bearing human B-cell lymphoma Ramos cells and inhibits tumor growth in BJAB xenograft model. In summary, MPT0E028 possesses strong in vitro and in vivo activity against malignant cells, representing a potential therapeutic approach for cancer therapy.
Keywords: Akt; B-cell lymphoma; MPT0E028; apoptosis; histone deacetylase (HDAC).