10058‑F4, a c‑Myc inhibitor, markedly increases valproic acid‑induced cell death in Jurkat and CCRF‑CEM T‑lymphoblastic leukemia cells

Mu,Qitian; Ma,Qiuling; Lu,Shasha; Zhang,Ting; Yu,Mengxia; Huang,Xin; Chen,Jian; Jin,Jie

doi:10.3892/ol.2014.2277

10058‑F4, a c‑Myc inhibitor, markedly increases valproic acid‑induced cell death in Jurkat and CCRF‑CEM T‑lymphoblastic leukemia cells

Authors:
- Qitian Mu
- Qiuling Ma
- Shasha Lu
- Ting Zhang
- Mengxia Yu
- Xin Huang
- Jian Chen
- Jie Jin
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Affiliations: Department of Hematology, Institute of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China
Published online on: June 24, 2014 https://doi.org/10.3892/ol.2014.2277
Pages: 1355-1359

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Abstract

Adult T‑cell acute lymphoblastic leukemia (T‑ALL) has a poor prognosis. Although it has been found that activation of Notch1 signaling occurs in >50% T‑ALL patients, γ‑secretase inhibitors that target Notch1 signaling are of limited efficacy. However, c‑Myc is an important direct target of Notch1 and, thus, c‑Myc is another potential therapeutic target for T‑ALL. Valproic acid (VPA), a histone deacetylase inhibitor, has been reported to treat various hematological malignancies. In the present study, we showed that c‑Myc expression, at a transcriptional level, was dose‑dependently downregulated in VPA‑induced growth inhibition in T‑ALL cell lines, Jurkat and CCRF‑CEM cells. 10058‑F4, a small molecule c‑Myc inhibitor, could increase the downregulation of c‑Myc and markedly increase the growth inhibition and cell death induced by VPA in Jurkat and CCRF‑CEM cells, which was accompanied by obvious cleavage of capase‑3. Z‑VAD‑FMK, a caspase inhibitor, partially prevented the anti‑leukemic effect. The results of the present study suggest that c‑Myc inhibitors increase cell death induced by VPA in a caspase‑dependent and ‑independent manner, and their combination could be a potent therapeutic strategy for adult T‑ALL patients.

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