Novel oral histone deacetylase inhibitor, MPT0E028, displays potent growth-inhibitory activity against human B-cell lymphoma in vitro and in vivo
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Han-Li Huang1, Chieh-Yu Peng2,3, Mei-Jung Lai4, Chun-Han Chen1, Hsueh-Yun Lee5, Jing-Chi Wang6, Jing-Ping Liou5, Shiow-Lin Pan6 and Che-Ming Teng1
1 Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
2 Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
3 School of Pharmacy, China Medical University, Taichung, Taiwan
4 Center for Translational Medicine, Taipei Medical University, Taipei, Taiwan
5 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
6 The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Che-Ming Teng, email:
Shiow-Lin Pan, email:
Jing-Ping Liou, email:
Keywords: MPT0E028, B-cell lymphoma, Histone deacetylase (HDAC), Akt, apoptosis
Received: October 15, 2014 Accepted: December 26, 2014 Published: December 31, 2014
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.
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