Document Detail

Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin.
MedLine Citation:
PMID:  16219763     Owner:  NLM     Status:  MEDLINE    
Allyl sulfides are characteristic flavor components obtained from garlic. These sulfides are thought to be responsible for their epidemiologically proven anticancer effect on garlic eaters. This study was aimed at clarifying the molecular basis of this anticancer effect of garlic by using human colon cancer cell lines HCT-15 and DLD-1. The growth of the cells was significantly suppressed by diallyl trisulfide (DATS, HCT-15 IC50 = 11.5 microM, DLD-1 IC50 = 13.3 microM); however, neither diallyl monosulfide nor diallyl disulfide showed such an effect. The proportion of HCT-15 and that of DLD-1 cells residing at the G1 and S phases were decreased by DATS, and their populations at the G2/M phase were markedly increased for up to 12 h. The cells with a sub-G1 DNA content were increased thereafter. Caspase-3 activity was also dramatically increased by DATS. Fluorescence-activated cell sorter analysis performed on the cells arrested at the G1/S boundary revealed cell cycle-dependent induction of apoptosis through the transition of the G2/M phase to the G1 phase by DATS. DATS inhibited tubulin polymerization in an in vitro cell-free system. DATS disrupted microtubule network formation of the cells, and microtubule fragments could be seen at the interphase. Peptide mass mapping by liquid chromatography-tandem mass spectrometry analysis for DATS-treated tubulin demonstrated that there was a specific oxidative modification of cysteine residues Cys-12beta and Cys-354beta to form S-allylmercaptocysteine with a peptide mass increase of 72.1 Da. The potent antitumor activity of DATS was also demonstrated in nude mice bearing HCT-15 xenografts. This is the first paper describing intracellular target molecules directly modified by garlic components.
Takashi Hosono; Tomomi Fukao; Jun Ogihara; Yoshimasa Ito; Hajime Shiba; Taiichiro Seki; Toyohiko Ariga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-12     Completed Date:  2006-02-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  41487-93     Citation Subset:  IM    
Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa 252-8510, Japan.
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MeSH Terms
Allyl Compounds / chemistry,  pharmacology*
Antineoplastic Agents / pharmacology*
Blotting, Western
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cell Separation
Cell-Free System
Chromatography, Liquid
Colonic Neoplasms / metabolism*
Cyclin B / metabolism
Cyclin B1
Cysteine / analogs & derivatives,  chemistry
Cytoplasm / metabolism
DNA / chemistry
Disulfides / chemistry
Flow Cytometry
Fluorescent Antibody Technique, Indirect
Inhibitory Concentration 50
Mice, Nude
Microtubules / metabolism,  ultrastructure
Neoplasm Transplantation
Oxidative Stress
Oxygen / chemistry
Peptides / chemistry
Protein Binding
Sulfides / chemistry,  pharmacology*
Time Factors
Tubulin / chemistry*
Reg. No./Substance:
0/Allyl Compounds; 0/Antineoplastic Agents; 0/CCNB1 protein, human; 0/Ccnb1 protein, mouse; 0/Cyclin B; 0/Cyclin B1; 0/Disulfides; 0/Peptides; 0/S-allylmercaptocysteine; 0/Sulfides; 0/Tubulin; 2050-87-5/diallyl trisulfide; 2179-57-9/diallyl disulfide; 52-90-4/Cysteine; 7782-44-7/Oxygen; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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