Synergistic targeting of Sp1, a critical transcription factor for myeloma cell growth and survival, by panobinostat and proteasome inhibitors

• Material Type: 博士論文
• ISSN: 1949-2553
• Title: Synergistic targeting of Sp1, a critical transcription factor for myeloma cell growth and survival, by panobinostat and proteasome inhibitors
• Volume: 7 48
• Author/Editor: Bat-Erdene, Ariunzaya; Miki, Hirokazu; Oda, Asuko; Nakamura, Shingen; Teramachi, Jumpei; Amachi, Ryota; Tenshin, Hirofumi; Hiasa, Masahiro; Iwasa, Masami; Harada, Takeshi; Fujii, Shiroh; Sogabe, Kimiko; Kagawa, Kumiko; Yoshida, Sumiko; Endo, Itsuro; Aihara, Kenichi; Abe, Masahiro
• Author Heading: Bat-Erdene, Ariunzaya; Miki, Hirokazu; Oda, Asuko; Nakamura, Shingen; Teramachi, Jumpei; Amachi, Ryota; Tenshin, Hirofumi; Hiasa, Masahiro; Iwasa, Masami; Harada, Takeshi; Fujii, Shiroh; Sogabe, Kimiko; Kagawa, Kumiko; Yoshida, Sumiko; Endo, Itsuro; Aihara, Kenichi; Abe, Masahiro
• Publication, Distribution, etc.: Impact Journals
• Publication Date: 2016-10-12
• Publication Date (W3CDTF): 2016-10-12
• Alternative Title: パノビノスタットとプロテアソーム阻害薬は骨髄腫細胞の増殖と生存に必須の転写因子Sp1を相乗的に標的にする
• Periodical title: Oncotarget
• Degree grantor/type: 徳島大学
• Date Granted: 2016-11-24
• Date Granted (W3CDTF): 2016-11-24
• Dissertation Number: 甲第3002号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3002号
• Text Language Code: eng
• Subject Heading: multiple myeloma; panobinostat; proteasome inhibitors; caspase-8; Sp1
• Target Audience: 一般
• Note (General): Panobinostat, a pan-deacetylase inhibitor, synergistically elicits cytotoxic activity against myeloma (MM) cells in combination with the proteasome inhibitor bortezomib. Because precise mechanisms for panobinostat’s anti-MM action still remain elusive, we aimed to clarify the mechanisms of anti-MM effects of panobinostat and its synergism with proteasome inhibitors. Although the transcription factor Sp1 was overexpressed in MM cells, the Sp1 inhibitor terameprocol induced MM cell death in parallel with reduction of IRF4 and cMyc. Panobinostat induced activation of caspase-8, which was inversely correlated with reduction of Sp1 protein levels in MM cells. The panobinostat-mediated effects were further potentiated to effectively induce MM cell death in combination with bortezomib or carfilzomib even at suboptimal concentrations as a single agent. Addition of the caspase-8 inhibitor z-IETD-FMK abolished the Sp1 reduction not only by panobinostat alone but also by its combination with bortezomib, suggesting caspase-8-mediated Sp1 degradation. The synergistic Sp1 reduction markedly suppressed Sp1-driven prosurvival factors, IRF4 and cMyc. Besides, the combinatory treatment reduced HDAC1, another Sp1 target, in MM cells, which may potentiate HDAC inhibition. Collectively, caspase-8-mediated post-translational Sp1 degradation appears to be among major mechanisms for synergistic anti-MM effects of panobinostat and proteasome inhibitors in combination.
• DOI: info:doi/10.18632/oncotarget.12594; https://doi.org/info:doi/10.18632/oncotarget.12594
• Persistent ID (NDL): info:ndljp/pid/10300269; https://dl.ndl.go.jp/pid/10300269
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-02-09T20:08:30+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/109988
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp