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Leuk Lymphoma. 2018 Jun;59(6):1439-1450. doi: 10.1080/10428194.2017.1376741. Epub 2017 Sep 18.

The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells.

Author information

1
a Department of Medicine, Division of Hematology and Rheumatology , Nihon University School of Medicine , Tokyo , Japan.
2
b Department of Biochemistry , Tokyo Medical University , Tokyo , Japan.

Abstract

The D-type cyclin (CCND)-cyclin-dependent kinase 4/6 (CDK4/6) complex has been implicated in multiple myeloma development. We investigated the biological activity of CDK4/6 inhibitor abemaciclib on cell growth and survival in three myeloma cell lines, KMS-12-PE, RPMI 8226, and IM-9. Abemaciclib inhibited myeloma cell growth in a dose-dependent manner in all cell lines, with significant differences seen at a concentration of 320 nM. Treatment with 1 μM abemaciclib increased the fraction of cells in the G0/G1 phase and decreased the fraction in the S-G2/M phases. Further, treatment with abemaciclib at a concentration of 3.2 μM or more showed apparent cytocidal activity accompanied with cytoplasmic vacuolization against myeloma cells. Importantly, abemaciclib induced autophagy in a dose-dependent manner in all three cell lines. These results indicate that the CCND-CDK4/6 complex is closely tied to myeloma cell growth and survival.

KEYWORDS:

Abemaciclib; autophagy; cell death; multiple myeloma

PMID:
28918692
DOI:
10.1080/10428194.2017.1376741
[Indexed for MEDLINE]

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