Journal
ONCOLOGY LETTERS
Volume 8, Issue 3, Pages 1355-1359Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2014.2277
Keywords
Jurkat; CCRF-CEM; valproic acid; c-Myc inhibitors; T-cell acute lymphoblastic leukemia; cell death
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Funding
- Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province [2011R50015]
- National Public Health Grand Research Foundation [201202017]
- Foundation of Ningbo Medical Science and Technology Project [2011A02]
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Adult T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis. Although it has been found that activation of Notchl signaling occurs in >50% T-ALL patients, gamma-secretase inhibitors that target Notchl signaling are of limited efficacy. However, c-Myc is an important direct target of Notchl 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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