Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Fungal Malformins Inhibit Bleomycin-Induced G2 Checkpoint in Jurkat Cells
Keiichi HagimoriTakashi FukudaYoko HasegawaSatoshi ŌmuraHiroshi Tomoda
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2007 Volume 30 Issue 8 Pages 1379-1383

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Abstract

A DNA-damaging agent, bleomycin, arrests the cell cycle at the G2 phase of Jurkat cells, which are defective in the G1 checkpoint, while microtubule-disrupting colchicine arrests it at M phase. Fungal cyclopeptides, malformin A1 and malformin C, were found to abrogate bleomycin-induced G2 arrest (IC50; 0.48 μM and 0.9 nM, respectively), resulting in a drastic decrease in cells in G2 phase and increase in cells in subG1 phase. On the other hand, malformins showed little effect on the colchicine-induced M phase arrest in Jurkat cells (IC50; 2.7 μM and 24 nM, respectively). Malformin C (0.026 μM) also abrogated bleomycin-induced G2 arrest in colon cancer-derived HCT-116 cells. These data strongly suggest that malformin C disrupted the cell cycle at the G2 checkpoint of cancer cells, leading to sensitization of the cancer cells to the anti-cancer reagent.

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© 2007 The Pharmaceutical Society of Japan
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