Document Detail

5,5-Diphenyl-2-thiohydantoin-N10 (DPTH-N10) suppresses proliferation of cultured colon cancer cell line COLO-205 by inhibiting DNA synthesis and activating apoptosis.
MedLine Citation:
PMID:  20449574     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to investigate the potential applications of 5,5-diphenyl-2-thiohydantoin-N10 (DPTH-N10) in the treatment of human colon cancer. Subcultured human colon cancer cell line, COLO-205, was used for examining the antiproliferation effect of DPTH-N10 on colon cancer. Thymidine incorporation and cell count were conducted to examine the antiproliferation effect of DPTH-N10. Western blot analysis was performed to examine the protein levels of cell cycle-related proteins. DNA fragmentation assay was performed to examine the occurrence of apoptosis. DPTH-N10 at a range of concentrations (0-30 microM) inhibits the proliferation but did not cause the cell death of COLO-205, indicating that it may have an inhibitory effect on the cell proliferation in COLO-205. The apoptosis was observed in COLO-205 when the DPTH-N10 concentrations were higher than 30 muM. Western blot analysis showed that the protein level of the cell cycle inhibitory protein, p21, in COLO-205 increased after DPTH-N10 treatment. Immunoprecipitation showed that the formation of the cyclin-dependent kinase (CDK)2-p21 complex was increased in the DPTH-N10-treated COLO-205. Kinase assay further demonstrated that the CDK2 activity was decreased in the DPTH-N10-treated COLO-205. DPTH-N10 caused growth inhibition in COLO-205 by inhibiting DNA synthesis and activating apoptosis. The findings from our previous in vitro studies in DPTH-N10-induced anti-angiogenic effect and from the present in vitro studies in DPTH-N10-induced antiproliferation effect on colon cancer cell line strongly suggest the potential applications of DPTH-N10 in the treatment of human colon cancer.
Tong-Sheng Lee; Li-Ching Chen; Yuan Liu; Jender Wu; Yu-Chih Liang; Wen-Sen Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-07
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  382     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-22     Completed Date:  2010-09-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  43-50     Citation Subset:  IM    
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
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MeSH Terms
Angiogenesis Inhibitors / administration & dosage,  pharmacology
Antineoplastic Agents / administration & dosage,  pharmacology*
Apoptosis / drug effects
Blotting, Western
Cell Line, Tumor
Cell Proliferation / drug effects
Colonic Neoplasms / drug therapy*,  pathology
Cyclin-Dependent Kinase Inhibitor p21 / drug effects,  metabolism
DNA / biosynthesis*
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Phenytoin / administration & dosage,  analogs & derivatives*,  pharmacology
Reg. No./Substance:
0/5,5-diphenyl-2-thiohydantoin-N10; 0/Angiogenesis Inhibitors; 0/Antineoplastic Agents; 0/Cyclin-Dependent Kinase Inhibitor p21; 57-41-0/Phenytoin; 9007-49-2/DNA

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