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

Noriyoshi Iriyama; Hirotsugu Hino; Shota Moriya; Masaki Hiramoto; Yoshihiro Hatta; Masami Takei; Keisuke Miyazawa

doi:10.1080/10428194.2017.1376741

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

Noriyoshi Iriyama, Hirotsugu Hino, Shota Moriya, Masaki Hiramoto, Yoshihiro Hatta, Masami Takei, Keisuke Miyazawa

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1439-1450
Number of pages	12
Journal	Leukemia and Lymphoma
Volume	59
Issue number	6
DOIs	https://doi.org/10.1080/10428194.2017.1376741
Publication status	Published - 3 Jun 2018
Externally published	Yes

Keywords

Abemaciclib
autophagy
cell death
multiple myeloma

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10.1080/10428194.2017.1376741

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

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",

author = "Noriyoshi Iriyama and Hirotsugu Hino and Shota Moriya and Masaki Hiramoto and Yoshihiro Hatta and Masami Takei and Keisuke Miyazawa",

note = "Publisher Copyright: {\textcopyright} 2017 Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2018",

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doi = "10.1080/10428194.2017.1376741",

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T1 - The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells

AU - Iriyama, Noriyoshi

AU - Hino, Hirotsugu

AU - Moriya, Shota

AU - Hiramoto, Masaki

AU - Hatta, Yoshihiro

AU - Takei, Masami

AU - Miyazawa, Keisuke

PY - 2018/6/3

Y1 - 2018/6/3

N2 - 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.

AB - 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.

KW - Abemaciclib

KW - autophagy

KW - cell death

KW - multiple myeloma

UR - https://www.scopus.com/pages/publications/85029592182

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DO - 10.1080/10428194.2017.1376741

M3 - Article

C2 - 28918692

AN - SCOPUS:85029592182

SN - 1042-8194

VL - 59

SP - 1439

EP - 1450

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 6

ER -

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

Abstract

Keywords

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