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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

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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 μM) 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 μM. 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.

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Abbreviations

CDK:

Cyclin-dependent kinase

DPH:

5,5-Diphenylhydantoin

DPTH-N10:

5,5-Diphenyl-2-thiohydantoin-N10

FBS:

Fetal bovine serum

HUVEC:

Human umbilical venous endothelial cells

MTT:

3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide

NP-40:

Nonident P-40

PMSF:

Phenylmethylsulphonyl fluoride

SDS:

Sodium dodecyl sulfate

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Acknowledgments

This work was supported by research grants from SKH-TMU-94-08, SKH-TMU-95-09, and the National Science Council of the Republic of China (NSC 97-2320-B-038-017).

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Authors and Affiliations

  1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan

    Tong-Sheng Lee, Li-Ching Chen, Yuan Liu & Wen-Sen Lee

  2. Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Tong-Sheng Lee

  3. Department of Ophthalmology, Cathay General Hospital, Taipei, Taiwan

    Tong-Sheng Lee

  4. Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan

    Jender Wu

  5. Department of Biomedical Technology, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yu-Chih Liang

  6. Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Wen-Sen Lee

  7. Cancer Research Center, Taipei Medical University and Hospital, Taipei, Taiwan

    Wen-Sen Lee

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  1. Tong-Sheng Lee
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  2. Li-Ching Chen
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  3. Yuan Liu
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  4. Jender Wu
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  5. Yu-Chih Liang
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Correspondence to Wen-Sen Lee.

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Lee, TS., Chen, LC., Liu, Y. et al. 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. Naunyn-Schmied Arch Pharmacol 382, 43–50 (2010). https://doi.org/10.1007/s00210-010-0519-4

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  • DOI: https://doi.org/10.1007/s00210-010-0519-4

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