Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 30, Issue 8, Pages 1379-1383Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.30.1379
Keywords
malformin C; G2 checkpoint inhibitor; cell cycle. anti-cancer agent; bleomycin; fungal metabolite
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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 A 1 and malformin C, were found to abrogate bleomycin-induced G2 arrest (IC50; 0.48 mu M 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 mu M and 24 nM, respectively). Malformin C (0.026 mu M) 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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