The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells.
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.
['Iriyama|Noriyoshi|N|', 'Hino|Hirotsugu|H|', 'Moriya|Shota|S|', 'Hiramoto|Masaki|M|', 'Hatta|Yoshihiro|Y|', 'Takei|Masami|M|', 'Miyazawa|Keisuke|K|']
D000631:Aminopyridines D017209:Apoptosis D001343:Autophagy D001562:Benzimidazoles D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D051358:Cyclin-Dependent Kinase 4 D051361:Cyclin-Dependent Kinase 6 D006801:Humans D009101:Multiple Myeloma D047428:Protein Kinase Inhibitors
Abemaciclib autophagy multiple myeloma cell death