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Int J Stem Cells. 2018 May 30;11(1):131-140. doi: 10.15283/ijsc18021.

The Bromodomain Inhibitor JQ1 Enhances the Responses to All-trans Retinoic Acid in HL-60 and MV4-11 Leukemia Cells.

Author information

1
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea.
2
Department of Immunology and Physiology, School of Medicine, Konkuk University, Seoul, Korea.
3
Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea.

Abstract

All-trans retinoic acid (ATRA) is a highly effective treatment for acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML). However, ATRA-based treatment is not effective in other subtypes of AML. In non-APL AML, ATRA signaling pathway is impaired or downmodulated, and consequently fails to respond to pharmacological doses of ATRA. Therefore, complementary treatment strategies are needed to improve ATRA responsiveness in non-APL AML. In this study, we investigated the combined effect of ATRA and bromodomain inhibitor JQ1, proven to have potent anti-cancer activity mainly through inhibition of c-Myc. We showed that the combination of ATRA with JQ1 synergistically inhibited proliferation of AML cells. The synergistic growth inhibition was resulted from differentiation or apoptosis depending on the kind of AML cells. Concomitantly, the combined treatment of ATRA and JQ1 caused greater depletion of c-Myc and hTERT expression than each agent alone in AML cells. Taken together, these findings support the rationale for the use of the combination of ATRA and JQ1 as a therapeutic strategy for the treatment of AML.

KEYWORDS:

Acute myeloid leukemia; All-trans retinoic acid; Apoptosis; Differentiation; JQ1; c-Myc

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