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.

Abstract

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.

• Authors: Tong-Sheng Lee, Li-Ching Chen, Yuan Liu, Jender Wu, Yu-Chih Liang, Wen-Sen Lee
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 382 Issue 1 Pg. 43-50 (Jul 2010) ISSN: 1432-1912 [Electronic] Germany
• PMID: 20449574 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5,5-diphenyl-2-thiohydantoin-N10
• Angiogenesis Inhibitors
• Antineoplastic Agents
• Cyclin-Dependent Kinase Inhibitor p21
• Phenytoin
• DNA

Topics

• 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
• Humans
• Phenytoin (administration & dosage, analogs & derivatives, pharmacology)