| The dynamin inhibitors MiTMAB and OcTMAB induce cytokinesis failure and inhibit cell proliferation in human cancer cells. | |
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MedLine Citation:
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PMID: 20571068 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The endocytic protein dynamin II (dynII) participates in cell cycle progression and has roles in centrosome cohesion and cytokinesis. We have described a series of small-molecule inhibitors of dynamin [myristyl trimethyl ammonium bromides (MiTMAB)] that competitively interfere with the ability of dynamin to bind phospholipids and prevent receptor-mediated endocytosis. We now report that dynII functions specifically during the abscission phase of cytokinesis and that MiTMABs exclusively block this step in the cell cycle. Cells treated with MiTMABs (MiTMAB and octadecyltrimethyl ammonium bromide) and dyn-depleted cells remain connected via an intracellular bridge for a prolonged period with an intact midbody ring before membrane regression and binucleate formation. MiTMABs are the first compounds reported to exclusively block cytokinesis without affecting progression through any other stage of the cell cycle. Thus, MiTMABs represent a new class of antimitotic compounds. We show that MiTMABs are potent inhibitors of cancer cell growth and have minimal effect on nontumorigenic fibroblast cells. Thus, MiTMABs have toxicity and antiproliferative properties that preferentially target cancer cells. This suggests that dynII may be a novel target for pharmacologic intervention for the treatment of cancer. |
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Authors:
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Sanket Joshi; Swetha Perera; Jayne Gilbert; Charlotte M Smith; Anna Mariana; Christopher P Gordon; Jennette A Sakoff; Adam McCluskey; Phillip J Robinson; Antony W Braithwaite; Megan Chircop |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-22 |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 9 ISSN: 1538-8514 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-09 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1995-2006 Citation Subset: IM |
Copyright Information:
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(c)2010 AACR. |
Affiliation:
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Children's Medical Research Institute, The University of Sydney, Westmead, New South Wales, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkanes
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pharmacology* Animals Cell Cycle / drug effects Cell Line Cell Line, Tumor Cell Proliferation / drug effects* Cell Survival / drug effects Cytokinesis / drug effects* Detergents / pharmacology Dose-Response Relationship, Drug Dynamins / antagonists & inhibitors*, genetics, metabolism Fibroblasts / cytology, drug effects, metabolism Flow Cytometry GTP Phosphohydrolases / antagonists & inhibitors, metabolism Hela Cells Humans Immunoblotting Mice Microscopy, Fluorescence NIH 3T3 Cells Quaternary Ammonium Compounds / pharmacology* RNA Interference Trimethyl Ammonium Compounds / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Alkanes; 0/Detergents; 0/Quaternary Ammonium Compounds; 0/Trimethyl Ammonium Compounds; 0/octadecyltrimethylammonium bromide; 10182-92-0/tetradecyltrimethylammonium; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.5.5/Dynamins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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