The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines

  • Authors:
    • Susanne Gahr
    • Gisela Peter
    • Thadäus Till Wissniowski
    • Eckhart G. Hahn
    • Christoph Herold
    • Matthias Ocker
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/or_00000137
  • Pages: 1249-1256
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Abstract

Effective therapies for advanced stages of hepatocellular carcinoma (HCC) have yet to be developed. We investigated how far a combination of the HDAC inhibitor MS-275 and the CDK inhibitor CYC-202 synergizes to inhibit proliferation and promotes apoptosis of hepatoma cells in vitro. Human hepatoma cell lines Hep3B and HepG2 as well as primary human foreskin fibroblasts as non-malignant controls were cultured under standardized conditions and incubated with increasing concentrations of CYC-202 and MS-275 as single agents and in combination. After 24 to 72 h, apoptosis was analyzed by flow cytometry (propidium iodide, JC-1) and by immunocytochemistry for cytokeratin 18 fragmentation. DNA synthesis was assessed using bromodeoxyuridine incorporation. Protein was separated for Western blotting against p21, bax and bcl-2 and fluorimetric activity assays against caspase 3 and 8. The results showed that the combination of CYC-202 and MS-275 leads to better pro-apoptotic effects than the employment of single substances. Apoptosis was induced via the mitochondrial pathway as evidenced by a shift in the bax/bcl-2 ratio and breakdown of mitochondrial transmembrane potentials. Caspase assays revealed a strong induction of caspase 3 but not of the extrinsic initiator caspase 8. In conclusion, combination therapy with the biomodulators MS-275 and CYC-202 is a promising treatment option for HCC.

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November 2008
Volume 20 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Gahr S, Peter G, Wissniowski TT, Hahn EG, Herold C and Ocker M: The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines. Oncol Rep 20: 1249-1256, 2008
APA
Gahr, S., Peter, G., Wissniowski, T.T., Hahn, E.G., Herold, C., & Ocker, M. (2008). The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines. Oncology Reports, 20, 1249-1256. https://doi.org/10.3892/or_00000137
MLA
Gahr, S., Peter, G., Wissniowski, T. T., Hahn, E. G., Herold, C., Ocker, M."The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines". Oncology Reports 20.5 (2008): 1249-1256.
Chicago
Gahr, S., Peter, G., Wissniowski, T. T., Hahn, E. G., Herold, C., Ocker, M."The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines". Oncology Reports 20, no. 5 (2008): 1249-1256. https://doi.org/10.3892/or_00000137