Hagimori Keiichi, Fukuda Takashi, Hasegawa Yoko, Omura Satoshi, Tomoda Hiroshi
Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
Biol Pharm Bull. 2007 Aug;30(8):1379-83. doi: 10.1248/bpb.30.1379.
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 microM 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 microM and 24 nM, respectively). Malformin C (0.026 microM) 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.
一种DNA损伤剂博来霉素可使Jurkat细胞的细胞周期停滞在G2期，这些细胞在G1期检查点存在缺陷，而破坏微管的秋水仙碱则使其停滞在M期。发现真菌环肽malformin A1和malformin C可消除博来霉素诱导的G2期停滞（IC50分别为0.48 microM和0.9 nM），导致G2期细胞急剧减少，亚G1期细胞增加。另一方面，malformins对秋水仙碱诱导的Jurkat细胞M期停滞影响很小（IC50分别为2.7 microM和24 nM）。Malformin C（0.026 microM）也可消除博来霉素诱导的结肠癌来源的HCT-116细胞的G2期停滞。这些数据强烈表明，malformin C在癌细胞的G2期检查点破坏了细胞周期，导致癌细胞对抗癌试剂敏感。
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