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Arsenic Trioxide Prevents Osteosarcoma Growth by Inhibition of GLI Transcription via DNA Damage Accumulation
http://hdl.handle.net/10232/19918
http://hdl.handle.net/10232/19918b685a662-4e58-4826-a316-1a770013b3cf
| 名前 / ファイル | ライセンス | アクション |
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Arsenic Trioxide Prevents Osteosarcoma Growth by Inhibition of GLI Transcription via DNA Damage Accumulation.pdf (2.4 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||
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| 公開日 | 2014-04-04 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Arsenic Trioxide Prevents Osteosarcoma Growth by Inhibition of GLI Transcription via DNA Damage Accumulation | |||||||||||
| タイトル言語 | en | |||||||||||
| 著者 |
中村, 俊介
× 中村, 俊介× 永野, 聡× 永尾, 宗子× 石堂, 康弘× 横内, 雅博× 棈松, 昌彦× 山元, 拓哉× 小宮, 節郎× 瀬戸口, 啓夫
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| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||
| 資源タイプ | journal article | |||||||||||
| 要約 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | The Hedgehog pathway is activated in various types of malignancies. We previously reported that inhibition of SMO or GLI prevents osteosarcoma growth in vitro and in vivo. Recently, it has been reported that arsenic trioxide (ATO) inhibits cancer growth by blocking GLI transcription. In this study, we analyzed the function of ATO in the pathogenesis of osteosarcoma. Real-time PCR showed that ATO decreased the expression of Hedgehog target genes, including PTCH1, GLI1, and GLI2, in human osteosarcoma cell lines. WST-1 assay and colony formation assay revealed that ATO prevented osteosarcoma growth. These findings show that ATO prevents GLI transcription and osteosarcoma growth in vitro. Flow cytometric analysis showed that ATO promoted apoptotic cell death. Comet assay showed that ATO treatment increased accumulation of DNA damage. Western blot analysis showed that ATO treatment increased the expression of γH2AX, cleaved PARP, and cleaved caspase-3. In addition, ATO treatment decreased the expression of Bcl-2 and Bcl-xL. These findings suggest that ATO treatment promoted apoptotic cell death caused by accumulation of DNA damage. In contrast, Sonic Hedgehog treatment decreased the expression of γH2AX induced by cisplatin treatment. ATO re-induced the accumulation of DNA damage attenuated by Sonic Hedgehog treatment. These findings suggest that ATO inhibits the activation of Hedgehog signaling and promotes apoptotic cell death in osteosarcoma cells by accumulation of DNA damage. Finally, examination of mouse xenograft models showed that ATO administration prevented the growth of osteosarcoma in nude mice. Because ATO is an FDA-approved drug for treatment of leukemia, our findings suggest that ATO is a new therapeutic option for treatment of patients with osteosarcoma. | |||||||||||
| 内容記述言語 | en | |||||||||||
| 収録雑誌名 |
en : PLoS ONE 巻 8, 号 7, 発行日 2013 |
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| 日付 | 2013-07-08 | |||||||||||
| 日付タイプ | Issued | |||||||||||
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| 収録物識別子タイプ | EISSN | |||||||||||
| ISSN | 19326203 | |||||||||||
| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| DOI | https://doi.org/10.1371/journal.pone.0069466 | |||||||||||
| 権利 | ||||||||||||
| 権利情報の言語 | en | |||||||||||
| 権利情報 | © 2013 Nakamura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||||||||
| 出版タイプ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
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| 主題Scheme | NDC | |||||||||||
| 主題 | 493.6 | |||||||||||
| 公開者・出版者 | ||||||||||||
| 出版者 | Public Library of Science | |||||||||||
| 出版者言語 | en | |||||||||||
