Leptolstatin from Streptomyces sp. SAM1595, a new gap phase-specific inhibitor of the mammalian cell cycle. I. Screening, taxonomy, purification and biological activities.
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- ABE KEIICHI
- Department of Agricultural Chemistry, Faculty of Agriculture, The University of Tokyo Present address: Suntory Institute for Biomedical Research
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- YOSHIDA MINORU
- Department of Agricultural Chemistry, Faculty of Agriculture, The University of Tokyo
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- HORINOUCHI SUEHARU
- Department of Agricultural Chemistry, Faculty of Agriculture, The University of Tokyo
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- BEPPU TERUHIKO
- Department of Agricultural Chemistry, Faculty of Agriculture, The University of Tokyo
書誌事項
- タイトル別名
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- I. SCREENING, TAXONOMY, PURIFICATION AND BIOLOGICAL ACTIVITIES
説明
Leptolstatin, a new inhibitor of the progression of Gl and G2 phases of the mammalian cell cycle, was discovered through a unique screening system, in which effects of microbial metabolites on the cell cycle progression of the cultured rat fibroblasts were monitored by flow cytometry. The new inhibitor was extracted from the fermentation broth of Streptomyces sp. SAM 1595 with ethyl acetate, and purified by silica gel column chromatography and HPLC. Leptolstatin showed a strong cytostatic effect on rat normal fibroblasts 3Y1 with an IC50 value of 0.4ng/ml, but its antimicrobial activity was very weak. A 24-hour treatment of the fibroblast cells with lOng/ml of leptolstatin caused an arrest at Gl or G2 phase, as determined by flow cytometry. When the G2-arrested cells were freed from leptolstatin, those containing 4C DNA entered a new S phase without intervening M phase, resulting in the formation of proliferative tetraploid cells.
収録刊行物
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- The Journal of Antibiotics
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The Journal of Antibiotics 46 (5), 728-734, 1993
公益財団法人 日本感染症医薬品協会