| Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells. | |
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MedLine Citation:
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PMID: 16170031 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously reported that the garlic-derived compound S-allylmercaptocysteine (SAMC) causes growth inhibition, mitotic arrest, and induction of apoptosis in SW480 human colon cancer cells by inducing microtubule depolymerization and c-Jun NH(2) terminus kinase-1 activation. In the present study, we compared the aforementioned effects of SAMC to those of a series of garlic-derived and other organosulfur compounds. Among the 10 compounds tested, only SAMC, diallyl disulfide (DADS), and S-trityl-L-cysteine (trityl-cys) cause significant inhibition of cell growth with IC(50) values of 150, 56, and 0.9 micromol/L, respectively. These three compounds also induce G(2)-M cell cycle arrest and apoptosis. Further studies reveal that, like SAMC, the garlic-derived compound DADS exerts antiproliferative effects by binding directly to tubulin and disrupting the microtubule assembly, thus arresting cells in mitosis and triggering mitochondria-mediated signaling pathways that lead to apoptosis. However, the synthetic compound trityl-cys exerts its effect on M-phase arrest and growth inhibition by mechanisms that involve spindle impairment but do not involve disruption of microtubule structure or dynamics. Furthermore, trityl-cys does not induce marked loss of mitochondrial membrane potential or release of cytochrome c, but it does induce caspase-3 activation and poly(ADP-ribose) polymerase cleavage. Structure-function analysis suggests that both the allyl and the disulfide moieties are important features for the antiproliferative effects of SAMC and DADS. These findings may be useful in the identification, synthesis, and development of organosulfur compounds that have anticancer activity. |
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Authors:
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Danhua Xiao; John T Pinto; Gregg G Gundersen; I Bernard Weinstein |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 4 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-09-19 Completed Date: 2006-01-04 Revised Date: 2007-11-14 |
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: 1388-98 Citation Subset: IM |
Affiliation:
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Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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metabolism,
pathology* Allyl Compounds / pharmacology Apoptosis / drug effects* Caspase 3 Caspases / metabolism Cell Division / drug effects Colonic Neoplasms / metabolism, pathology* Cytochromes c / metabolism Enzyme Activation / drug effects Garlic / chemistry Humans Membrane Potentials / drug effects Microtubules / drug effects, metabolism Mitochondria / drug effects Mitosis / drug effects* Poly(ADP-ribose) Polymerases / metabolism Sulfur Compounds / pharmacology* Tubulin / metabolism Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA89815/CA/NCI NIH HHS; GM062938/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Allyl Compounds; 0/Sulfur Compounds; 0/Tubulin; 9007-43-6/Cytochromes c; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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