期刊
CHEMISTRY & BIOLOGY
卷 18, 期 6, 页码 743-751出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2011.03.012
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Grants-in-Aid for Scientific Research [22681034, 221S0001] Funding Source: KAKEN
BNS-22, a chemically synthesized derivative of the natural plant product GUT-70, has antiproliferative activity against human cancer cells, the mechanism of which is unknown. Here, we identify a target of BNS-22 by proteomic profiling analysis, which suggests that BNS-22 belongs to the same cluster as ICRF-193, a DNA topoisomerase II (TOP2) catalytic inhibitor. BNS-22 inhibits kinetoplast DNA decatenation that is mediated by human TOP2 alpha and TOP2 beta in vitro at an IC50 of 2.8 and 0.42 mu M respectively. BNS-22 does not affect DNA damage and antagonizes TOP2 poison-mediated DNA damage. Like ICRF-193, BNS-22 induces mitotic abnormalities, characterized by impairments in chromosome alignment and segregation, thereby causing polyploidy in HeLa cells. These results indicate that BNS-22 targets TOP2 and acts as its catalytic inhibitor.
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