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标题：Potentiation of Bleomycin in Jurkat Cells by Fungal Pycnidione
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作者：Mayumi Kaneko ; Daisuke Matsuda ; Masaki Ohtawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2012
卷号：35
期号：1
页码：18-28
DOI：10.1248/bpb.35.18
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：pycnidione;G2 arrest;bleomycin