Fungal malformins inhibit bleomycin-induced G2 checkpoint in Jurkat cells.
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.
Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
Keiichi
K
Hagimori
Takashi
T
Fukuda
Yoko
Y
Hasegawa
Satoshi
S
Omura
Hiroshi
H
Tomoda
D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001234:Aspergillus niger / Q000187:drug effects / Q000378:metabolism; D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D042846:CDC2-CDC28 Kinases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003078:Colchicine / Q000494:pharmacology; D003470:Culture Media / Q000737:chemistry; D005342:Fibrinolysis / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D010456:Peptides, Cyclic; D011500:Protein Synthesis Inhibitors; D001761:Bleomycin; C001675:malformins; D042846:CDC2-CDC28 Kinases; D003078:Colchicine