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Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences
http://hdl.handle.net/2241/00146446
http://hdl.handle.net/2241/00146446b0fa63ac-daa3-4e2b-be7a-7bd502874a01
名前 / ファイル | ライセンス | アクション |
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CD&D_2017-8 (4.7 MB)
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Item type | Journal Article(1) | |||||
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公開日 | 2017-06-12 | |||||
タイトル | ||||||
タイトル | Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Yu, Yue
× Yu, Yue× Katiyar, Shashank P× Sundar, Durai× Kaul, Zeenia× Miyako, Eijiro× Zhang, Zhenya× Kaul, Sunil C× Reddel, Roger R× Wadhwa, Renu |
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著者別名 |
張, 振亜
× 張, 振亜 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers). Withaferin-A (Wi-A), a major constituent of the medicinal plant, Withania somnifera (Ashwagandha), has been shown to exert anti-tumour activity. However, its effect on either telomerase or ALT mechanisms has not been investigated. Here, by using isogenic cancer cells with/without telomerase, we found that Wi-A caused stronger cytotoxicity to ALT cells. It was associated with inhibition of ALT-associated promyelocytic leukemia nuclear bodies, an established marker of ALT. Comparative analyses of telomerase positive and ALT cells revealed that Wi-A caused stronger telomere dysfunction and upregulation of DNA damage response in ALT cells. Molecular computational and experimental analyses revealed that Wi-A led to Myc-Mad mediated transcriptional suppression of NBS-1, an MRN complex protein that is an essential component of the ALT mechanism. The results suggest that Wi-A could be a new candidate drug for ALT cancers. | |||||
書誌情報 |
Cell Death and Disease 巻 8, p. e2755, 発行日 2017-04 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2041-4889 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 28425984 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/cddis.2017.33 | |||||
権利 | ||||||
権利情報 | © The Author(s) 2017 | |||||
権利 | ||||||
権利情報 | Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |||||
著者版フラグ | ||||||
値 | publisher | |||||
出版者 | ||||||
出版者 | Nature Publishing Group |