YM155 exerts potent cytotoxic activity against quiescent (G0/G1) multiple myeloma and bortezomib resistant cells via inhibition of survivin and Mcl-1

Material type: 文書・図像類

Author: Ookura, Miyukiほか

Publisher: Impact Journals

Publication date: 2017-12-04

Material Format: Digital

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Note (General)：: YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against...

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Material Type: 文書・図像類
Title: YM155 exerts potent cytotoxic activity against quiescent (G0/G1) multiple myeloma and bortezomib resistant cells via inhibition of survivin and Mcl-1
Author/Editor: Ookura, Miyuki
Fujii, Tatsuya
Yagi, Hideki
Ogawa, Takuya
Kishi, Shinji
Hosono, Naoko
Shigemi, Hiroko
Yamauchi, Takahiro
Ueda, Takanori
Yoshida, Akira
Author Heading: Ookura, Miyuki
Fujii, Tatsuya
Yagi, Hideki
Ogawa, Takuya
Kishi, Shinji
Hosono, Naoko
Shigemi, Hiroko
Yamauchi, Takahiro
Ueda, Takanori
Yoshida, Akira
Publication, Distribution, etc.: Impact Journals
Publication Date: 2017-12-04
Publication Date (W3CDTF): 2017-12-04
Periodical title: Oncotarget
No. or year of volume/issue: 8 67
Volume: 8
Issue: 67
Pages: 111535-111550
Text Language Code: eng
Subject Heading: YM155
survivin
Mcl-1
quiescent cells
multiple myeloma
Target Audience: 一般
Note (General): YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma activity in mouse xenograft model. YM155 suppressed the expression of survivin and rapidly directed Mcl-1 protein for proteasome degradation. YM155 abrogated the interleukin-6-induced STAT3 phosphorylation, subsequently blocked Mcl-1 expression and induced apoptosis in MM cells. Triple-color flow cytometric analysis revealed that YM155 potently induced cell death of MM cells in G0 phase. Quiescent primary MM cells were also sensitive to YM155. We established bortezomib-resistant MM cell line, U266/BTZR1, which possess a point mutation G322A. YM155 exhibited similar cytotoxic potency against U266/BTZR1 compared with parental cells. Interestingly, survivin expression was markedly elevated in U266/BTZR1 cells. Treatment with YM155 significantly down-regulated this increased survivin and Mcl-1 expression in U266/BTZR1 cells. In conclusion, our data indicate that YM155 exhibits potent cytotoxicity against quiescent (G0/G1) MM cells and bortezomib-resistant cells. These unique features of YM155 may be beneficial for the development of new therapeutic strategies to eliminate quiescent MM cells and overcome bortezomib resistance.
Source: https://u-fukui.repo.nii.ac.jp/?action=repository_action_common_download&item_id=23888&item_no=1&attribute_id=22&file_no=1
https://u-fukui.repo.nii.ac.jp/?action=repository_action_common_download&item_id=23888&item_no=1&attribute_id=22&file_no=1
Access Restrictions: 限定公開
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 福井大学 : 福井大学学術機関リポジトリ