ID 112919
タイトル別表記
Anti-myeloma Activity by Thiazolidine-2,4-dione compounds
著者
Oda, Asuka Tokushima University
Bat‐Erdene, Ariunzaya Tokushima University
Maeda, Yusaku Tokushima University
Takahashi, Mamiko Tokushima University
Iwasa, Masami Tokushima University
キーワード
multiple myeloma
PIM2
thiazolidine‐2
4‐dione compounds
breast cancer resistance protein
proteasome inhibitor
資料タイプ
学術雑誌論文
抄録
Pim-2 kinase is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of Pim inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced Pim-2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of Pim inhibitors, including AZD1208, CX-6258 and PIM447. SMI-16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations, and reduced in vitro colony forming capacity and in vivo tumorigenic activity in MM cells, suggesting impairment of their clonogenic capacity. Pim-2 is known to be subject to ubiquitination-independent proteasomal degradation. Consistently, the proteasome inhibitors bortezomib and carfilzomib increased Pim-2 protein levels in MM cells without affecting its mRNA levels. However, SMI-16a mitigated the Pim-2 protein increase and cooperatively enhanced anti-MM effects in combination with carfilzomib. Collectively, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a uniquely reduce Pim-2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned.
掲載誌名
British Journal of Haematology
ISSN
13652141
00071048
cat書誌ID
AA11618011
AA00574570
出版者
John Wiley & Sons Ltd
180
2
開始ページ
246
終了ページ
258
発行日
2018-01-12
備考
This is the peer reviewed version of the following article: Fujii, S. , Nakamura, S. , Oda, A. , Miki, H. , Tenshin, H. , Teramachi, J. , Hiasa, M. , Bat‐Erdene, A. , Maeda, Y. , Oura, M. , Takahashi, M. , Iwasa, M. , Endo, I. , Yoshida, S. , Aihara, K. , Kurahashi, K. , Harada, T. , Kagawa, K. , Nakao, M. , Sano, S. and Abe, M. (2018), Unique anti‐myeloma activity by thiazolidine‐2,4‐dione compounds with Pim inhibiting activity. Br J Haematol, 180: 246-258, which has been published in final form at https://doi.org/10.1111/bjh.15033. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
病院
医学系
歯学系
薬学系