Fungal Malformins Inhibit Bleomycin-Induced G2 Checkpoint in Jurkat Cells(Highlighted paper selected by Editor-in-chief,Biochemistry)

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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 (IC_<50>; 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 (IC_<50>; 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.
2007-08-01