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Article

Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro

  • Authors:
    • Christoph W. Strey
    • Lea Schamell
    • Elsie Oppermann
    • Axel Haferkamp
    • Wolf O. Bechstein
    • Roman A. Blaheta
  • View Affiliations / Copyright

    Affiliations: Department of General and Visceral Surgery, Johann Wolfgang Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany, Department of Urology, Johann Wolfgang Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany
  • Pages: 301-307
    |
    Published online on: January 20, 2011
       https://doi.org/10.3892/etm.2011.202
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Abstract

Valproate (VPA) is a well-characterized histone deacetylase inhibitor with anti-neoplastic properties. We analyzed the growth blocking effects and the molecular mode of action of this compound in colorectal cancer cells in vitro and in vivo. Caco-2, SW-480, CX-1 or WIDR cell lines were exposed to VPA (0.25-2 mM) for various time periods. Cell growth, cell cycle progression and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide dye reduction assay and flow cytometry. Cell cycle- and apoptosis-regulating proteins and histone acetylation were assessed by Western blotting. In vivo tumor growth and regulating protein expression under VPA were investigated in a subcutaneous xenograft tumor model. VPA inhibited the growth of all cell lines with cell cycle arrest paralleled by the up-regulation of H3 and H4 acetylation. In vivo tumor growth was substantially depressed by VPA (200 mg/kg bw). Cell cycle proteins (cdk1, cdk2, cdk4, cyclin D, cyclin E, p19, p21 and p27) were differentially altered by VPA. Predominantly cdk1 was decreased and p27 was up-regulated in all models. Apoptosis-related proteins were altered in vivo with up-regulation of bax and down-regulation of bcl-2. VPA exerts anti-neoplastic activity in colorectal tumor cell lines in vitro and in vivo by altering cell cycle regulation.
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Copy and paste a formatted citation
Spandidos Publications style
Strey CW, Schamell L, Oppermann E, Haferkamp A, Bechstein WO and Blaheta RA: Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro. Exp Ther Med 2: 301-307, 2011.
APA
Strey, C.W., Schamell, L., Oppermann, E., Haferkamp, A., Bechstein, W.O., & Blaheta, R.A. (2011). Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro. Experimental and Therapeutic Medicine, 2, 301-307. https://doi.org/10.3892/etm.2011.202
MLA
Strey, C. W., Schamell, L., Oppermann, E., Haferkamp, A., Bechstein, W. O., Blaheta, R. A."Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro". Experimental and Therapeutic Medicine 2.2 (2011): 301-307.
Chicago
Strey, C. W., Schamell, L., Oppermann, E., Haferkamp, A., Bechstein, W. O., Blaheta, R. A."Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro". Experimental and Therapeutic Medicine 2, no. 2 (2011): 301-307. https://doi.org/10.3892/etm.2011.202
Copy and paste a formatted citation
x
Spandidos Publications style
Strey CW, Schamell L, Oppermann E, Haferkamp A, Bechstein WO and Blaheta RA: Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro. Exp Ther Med 2: 301-307, 2011.
APA
Strey, C.W., Schamell, L., Oppermann, E., Haferkamp, A., Bechstein, W.O., & Blaheta, R.A. (2011). Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro. Experimental and Therapeutic Medicine, 2, 301-307. https://doi.org/10.3892/etm.2011.202
MLA
Strey, C. W., Schamell, L., Oppermann, E., Haferkamp, A., Bechstein, W. O., Blaheta, R. A."Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro". Experimental and Therapeutic Medicine 2.2 (2011): 301-307.
Chicago
Strey, C. W., Schamell, L., Oppermann, E., Haferkamp, A., Bechstein, W. O., Blaheta, R. A."Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro". Experimental and Therapeutic Medicine 2, no. 2 (2011): 301-307. https://doi.org/10.3892/etm.2011.202
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