Potentiation of Bleomycin in Jurkat Cells by Fungal Pycnidione
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概要
- 論文の詳細を見る
Most cancer cells have mutations in genes at the G1 checkpoint and repair DNA only in the G2 phase; therefore, the G2 checkpoint is a potential target to develop novel therapy. In the course of screening, a known compound, pycnidione, was isolated from the fungal culture broth of Gloeotinia sp. FKI-3416. Pycnidione irreversibly abrogated bleomycin-induced G2 arrest in Jurkat cells and synergically potentiated the cytotoxicity of bleomycin. To elucidate the mechanism of action, the effect of pycnidione on the signal transduction of the G2 checkpoint was analyzed, showing that the increased phospho-cyclin dependent kinase-1 (CDK1) level caused by bleomycin was abrogated in the presence of pycnidione, indicating that cells did not arrest at the G2 phase. Moreover, under these conditions, Chk1 and Chk2 levels were markedly down-regulated. Thus, we concluded that pycnidione abrogated bleomycin-induced G2 arrest by decreasing Chk1 and Chk2.
- 公益社団法人 日本薬学会の論文
著者
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Yamori Takao
Division Of Experimental Chemotherapy Cancer Chemotherapy Center Japanese Foundation For Cancer
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FUKUDA Takashi
Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, Kitasato Unive
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Ohtawa Masaki
School Of Pharmacy Kitasato University
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Matsuda Daisuke
Graduate School Of Pharmaceutical Sciences Kitasato University
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Tomoda Hiroshi
Graduate School Of Pharmaceutical Sciences Kitasato University
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Ohtawa Masaki
Graduate School of Pharmaceutical Sciences, Kitasato University
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Nagamitsu Tohru
Graduate School of Pharmaceutical Sciences, Kitasato University
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Kaneko Mayumi
Graduate School of Pharmaceutical Sciences, Kitasato University
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Tomoda Hiroshi
Graduate School Of Pharmaceutical Sciences Kitasato Univ.
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Fukuda Takashi
Kitasato Inst. For Life Sciences And Graduate School Of Infection Control Sciences Kitasato Univ.
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Matsuda Daisuke
Graduate School of Pharmaceutical Sciences, Kitasato University
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Tomoda Hiroshi
Graduate School of Pharmaceutical Science, Kitasato University
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