Dinaciclib reduces MCL-1 levels and triggers apoptosis in adult T-cell leukemia/lymphoma
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Issued Date
2026-03-28
Resource Type
ISSN
00142999
eISSN
18790712
Scopus ID
2-s2.0-105031235870
Journal Title
European Journal of Pharmacology
Volume
1019
Rights Holder(s)
SCOPUS
Bibliographic Citation
European Journal of Pharmacology Vol.1019 (2026)
Suggested Citation
Sittithumcharee G., Kariya R., Jirawatnotai S., Okada S. Dinaciclib reduces MCL-1 levels and triggers apoptosis in adult T-cell leukemia/lymphoma. European Journal of Pharmacology Vol.1019 (2026). doi:10.1016/j.ejphar.2026.178699 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115567
Title
Dinaciclib reduces MCL-1 levels and triggers apoptosis in adult T-cell leukemia/lymphoma
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Abstract
Adult T-cell leukemia/lymphoma (ATL) is a rare T-cell malignancy caused by long-term HTLV-1 infection. The disease is aggressive, with a median survival of 8-10 months, and no new treatments are currently available. Dinaciclib is a selective small-molecule drug that targets CDK1, CDK2, CDK5, and CDK9. This study assessed dinaciclib's ability to inhibit ATL cells. It significantly suppressed ATL proliferation at low nanomolar concentrations. The antiproliferative effect was due to induced apoptotic cell death, as shown by FACS analysis. Annexin/PI staining revealed morphological signs of apoptosis after dinaciclib treatment, while pre-treatment with Q-VD-OPh prevented apoptosis in ATL cells. The primary mechanism by which dinaciclib induces apoptosis appears to involve deregulation of anti-apoptotic proteins, especially MCL-1. MCL-1 protein levels decreased significantly in a dose- and time-dependent manner, coinciding with caspase-3 activation. The anti-tumor effects of dinaciclib were confirmed in an in vivo xenograft model. Overall, this study demonstrates that dinaciclib effectively targets ATL cells by inducing MCL-1 deregulation and promoting apoptotic cell death.