BET bromodomain inhibitor JQ1 decreases CD30 and CCR4 expression and proliferation of cutaneous T-cell lymphoma cell lines

Abstract

Bromodomain and external domain (BET) proteins regulate cell growth, proliferation, cell cycle, and differentiation in various cancers. Therefore, they have emerged as interesting targets. The effect of BET inhibitor on cutaneous T-cell lymphoma (CTCL), however, is yet to be known. Here, we examined the effect of BET inhibitor JQ1 on four cell lines (MyLa, SeAx, Hut78 and HH cells). CTCL cell lines were treated with JQ1 and cell number, cell cycle, frequency of apoptosis, and expressions of CD25, CD30 and CCR4 on the cell surface were evaluated by flow cytometry. Cell surface molecules were also analyzed by quantitative RT-PCR. JQ1 dose-dependently decreased the cell number of CTCL cells through G1 arrest concomitantly with downregulation of c-Myc expression. JQ1 induced senescence in MyLa cells and apoptosis in Hut78 and HH cells. We also showed that JQ1 inhibited tumor growth of HH cells in vivo. Moreover, JQ1 downregulated CD30 and CCR4 expression both on the cell surface and at mRNA levels. Thus, BET bromodomain inhibitor JQ1 may be useful for treatment of CTCL.

Keywords: BET bromodomain inhibitor; Cutaneous T-cell lymphoma; JQ1; Mycosis fungoides.