| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-01-26 |
| タイトル |
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タイトル |
Discovery of novel DNA-damaging agents through phenotypic screening for DNA double-strand break. |
|
言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Doudou Zhang
Takashi Shimokawa
Qianqian Guo
Shingo Dan
Yoshio Miki
Shigeaki Sunada
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
DNA double-strand breaks (DSBs) seriously damage DNA and promote genomic instability that can lead to cell death. They are the source of conditions such as carcinogenesis and aging, but also have important applications in cancer therapy. Therefore, rapid detection and quantification of DSBs in cells are necessary for identifying carcinogenic and anticancer factors. In this study, we detected DSBs using a flow cytometry-based high-throughput method to analyze γH2AX intensity. We screened a chemical library containing 9600 compounds and detected multiple DNA-damaging compounds, although we could not identify mechanisms of action through this procedure. Thus, we also profiled a representative compound with the highest DSB potential, DNA-damaging agent-1 (DDA-1), using a bioinformatics-based method we termed "molecular profiling." Prediction and verification analysis revealed DDA-1 as a potential inhibitor of topoisomerase IIα, different from known inhibitors such as etoposide and doxorubicin. Additional investigation of DDA-1 analogs and xenograft models suggested that DDA-1 is a potential anticancer drug. In conclusion, our findings established that combining high-throughput DSB detection and molecular profiling to undertake phenotypic analysis is a viable method for efficient identification of novel DNA-damaging compounds for clinical applications. |
| 書誌情報 |
Cancer science
巻 114,
号 3,
p. 1108-1117,
発行日 2022-11
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| 出版者 |
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出版者 |
Wiley Publishing on behalf of the Japanese Cancer Association |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1349-7006 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
36385507 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1111/cas.15659 |
