| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Satoshi Yamakawa; Aya Demizu; Yasuyuki Kawaratani; Yasuo Nagaoka; Yuji Terada; Sakiko Maruyama; Shinichi Uesato |
Related Documents
:
|
11036198 - Post-translational reduction of cell surface expression of insulin receptors by cyclosp... 12871588 - Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reduci... 6163528 - Discordant synthesis and secretion of human chorionic gonadotropin and subunits by cerv... 12539558 - Effect of transforming growth factor-beta 2 on phagocytosis in cultured bovine trabecul... 19888908 - Regulation of heme synthesis and proteasomal activity by copper: possible implications ... 7316228 - Changes in the surface morphologies of the cells in the bursa cloacalis (bursa of fabri... |
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 |
Affiliation:
|
Department of Life Science and Biotechnology, Faculty of Chemistry, Material and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aniline Compounds
/
pharmacology* Antineoplastic Agents / pharmacology* Apoptosis / drug effects Benzimidazoles 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 Humans Immunoprecipitation In Situ Nick-End Labeling JNK Mitogen-Activated Protein Kinases / physiology beta Catenin / metabolism |
| Chemical | |
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 2.7.11.24/JNK Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Re-evaluation of the antioxidant prenylated flavonoids from the roots of Sophora flavescens.
Next Document: The stimulatory activities of polysaccharide compounds derived from algae extracts on insulin secret...