Document Detail

Fungal malformins inhibit bleomycin-induced G2 checkpoint in Jurkat cells.
MedLine Citation:
PMID:  17666789     Owner:  NLM     Status:  MEDLINE    
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.
Keiichi Hagimori; Takashi Fukuda; Yoko Hasegawa; Satoshi Omura; Hiroshi Tomoda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  30     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-01     Completed Date:  2007-09-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1379-83     Citation Subset:  IM    
Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
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MeSH Terms
Antibiotics, Antineoplastic / antagonists & inhibitors*,  pharmacology
Aspergillus niger / drug effects,  metabolism
Bleomycin / antagonists & inhibitors*,  pharmacology
CDC2-CDC28 Kinases / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Colchicine / pharmacology
Culture Media / chemistry
Fibrinolysis / drug effects
G2 Phase / drug effects*
Jurkat Cells
Peptides, Cyclic / isolation & purification,  pharmacology*
Protein Synthesis Inhibitors / pharmacology*
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Culture Media; 0/Peptides, Cyclic; 0/Protein Synthesis Inhibitors; 11056-06-7/Bleomycin; 3022-92-2/malformins; 64-86-8/Colchicine; EC Kinases

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