Modulation of growth and differentiation of human colon carcinoma cells by histone deacetylase inhibitory trichostatins

Li,X; Yoshida,M; Beppu,T; Lotan,R

doi:10.3892/ijo.8.3.431

March 1996 Volume 8 Issue 3

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March 1996 Volume 8 Issue 3

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Article

Modulation of growth and differentiation of human colon carcinoma cells by histone deacetylase inhibitory trichostatins

Authors:
- X Li
- M Yoshida
- T Beppu
- R Lotan
View Affiliations / Copyright

Affiliations: UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT TUMOR BIOL 108,HOUSTON,TX 77030. UNIV TOKYO,DEPT BIOTECHNOL,TOKYO 113,JAPAN.
Pages: 431-437
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Published online on: March 1, 1996

https://doi.org/10.3892/ijo.8.3.431
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Abstract

Histone deacetylase inhibitors such as sodium butyrate or (R)-trichostatin A {(R)-TSA; 7- [4-(dimethylamino) phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-2, 4-heptadienamide} have been reported to modulate the proliferation and differentiation of certain cell types. In this study, we analyzed the effects of these agents on KM12 human colon carcinoma (HCC) cells in culture. We found that (R)-TSA induced cell flattening, inhibited anchorage-dependent and anchorage-independent growth, increased the level of the differentiation marker carcinoembryonic antigen, and increased the expression of gelsolin, a candidate tumor suppressor, in these HCC cells. Cells treated with (R)-TSA for 3 h exhibited a high degree of histone (primarily H4) acetylation. (R)-TSA exerted these effects at concentrations in the range between 0.1 to 1 mu M that are at least 1,000 times lower than those required to achieve similar effects by n-butyrate. Trichostatin C, which exhibits some histone deacetylase inhibitory activity but not the analogs (S)-TSA or (R)- or (S)-trichostatic acid, which lack histone deacetylase inhibitory activity, also showed some growth inhibitory activity. These results indicate that histone deacetylase inhibitors may lead to suppression of the transformed phenotype and enhanced differentiation in the KM12 HCC cells.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Modulation of growth and differentiation of human colon carcinoma cells by histone deacetylase inhibitory trichostatins

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Abstract

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