Document Detail

Growth inhibition of human colon cancer cell line HCT116 by bis[2-(acylamino)phenyl] disulfide and its action mechanism.
MedLine Citation:
PMID:  18451518     Owner:  NLM     Status:  MEDLINE    
Our laboratory has been investigating the use of compounds which disrupt beta-catenin/T cell factor (TCF) binding to treat human colon cancer. There are several cysteine residues on the surface of beta-catenin where it binds to TCF. Some bis[2-(acylamino)phenyl] disulfides might have the ability to form a disulfide bond with the cysteine residues of beta-catenin, leading to inhibition of the growth of human colon cells. Bis[2-(acylamino)phenyl] disulfides were screened to inhibit the growth of cancer cells. Among them, bis[2-(2,2-dimethylpropanoylamino)phenyl] disulfide (1) had promising inhibitory effects (HCT116, IC50: 9.7 microM; DLD-1, IC50: 6.9 microM) on cell proliferation, and did not show any cytotoxicity among normal human fibroblast CCD-1059SK cells even at 200 microM. This derivative reduced the beta-catenin/TCF4 association in the HCT116 cells to ca. 50% at 150 microM. Furthermore, it activated markedly the phosphorylation of c-Jun N-terminal kinase (JNK) connected to stress-activated apoptosis at a lower concentration (30 microM). In view of cell cycle analyses, Hoechst staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick end-labeling (TUNEL) assays along with the above results, it is likely that 1 inhibited the growth of HCT116 cells through pathways including the JNK-mediated apoptosis.
Satoshi Yamakawa; Aya Demizu; Yasuyuki Kawaratani; Yasuo Nagaoka; Yuji Terada; Sakiko Maruyama; Shinichi Uesato
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  31     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-02     Completed Date:  2008-06-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  916-20     Citation Subset:  IM    
Department of Life Science and Biotechnology, Faculty of Chemistry, Material and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan.
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MeSH Terms
Aniline Compounds / pharmacology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Blotting, Western
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Cyclin D1 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Disulfides / pharmacology*
Flow Cytometry
Fluorescent Dyes
HCT116 Cells
In Situ Nick-End Labeling
JNK Mitogen-Activated Protein Kinases / physiology
beta Catenin / metabolism
Reg. No./Substance:
0/Aniline Compounds; 0/Antineoplastic Agents; 0/Benzimidazoles; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Disulfides; 0/Fluorescent Dyes; 0/beta Catenin; 0/bis(2-(2,2-dimethylpropanoylamino)phenyl)disulfide; 136601-57-5/Cyclin D1; 23491-52-3/HOE 33342; EC Mitogen-Activated Protein Kinases

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

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