Display options
Cite
Strey CW, Schamell L, Oppermann E, et al. Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro. Exp Ther Med. 2011;2(2):301-307doi: 10.3892/etm.2011.202.
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(2), 301-307. https://doi.org/10.3892/etm.2011.202
Strey, Christoph W, et al. "Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro." Experimental and therapeutic medicine vol. 2,2 (2011): 301-307. doi: https://doi.org/10.3892/etm.2011.202
Strey CW, Schamell L, Oppermann E, Haferkamp A, Bechstein WO, Blaheta RA. Valproate inhibits colon cancer growth through cell cycle modification in vivo and in vitro. Exp Ther Med. 2011 Mar;2(2):301-307. doi: 10.3892/etm.2011.202. Epub 2011 Jan 20. PMID: 22977502; PMCID: PMC3440661.
Copy Download .nbib Format: NLM
Share it on

Exp Ther Med. 2011 Mar;2(2):301-307. doi: 10.3892/etm.2011.202. Epub 2011 Jan 20.

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

Experimental and therapeutic medicine

Christoph W Strey, Lea Schamell, Elsie Oppermann, Axel Haferkamp, Wolf O Bechstein, Roman A Blaheta

Affiliations

  1. Departments of General and Visceral Surgery, and.

PMID: 22977502 PMCID: PMC3440661 DOI: 10.3892/etm.2011.202

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.

References

  1. Oncogene. 2002 May 9;21(20):3207-12 - PubMed
  2. Cancer. 2007 Sep 1;110(5):943-54 - PubMed
  3. J Cell Sci. 2008 Dec 1;121(Pt 23):3853-7 - PubMed
  4. Am J Physiol Renal Physiol. 2010 Feb;298(2):F426-34 - PubMed
  5. Genes Dev. 1999 Jun 15;13(12):1501-12 - PubMed
  6. Cancer Res. 2004 Feb 1;64(3):1079-86 - PubMed
  7. J Biol Chem. 2005 Dec 23;280(51):42433-41 - PubMed
  8. EMBO J. 2001 Dec 17;20(24):6969-78 - PubMed
  9. J Biol Chem. 2010 Apr 2;285(14):10678-89 - PubMed
  10. J Cell Mol Med. 2009 Aug;13(8B):2376-2385 - PubMed
  11. Cell. 2001 May 4;105(3):297-306 - PubMed
  12. Clin Cancer Res. 2008 Mar 15;14(6):1669-77 - PubMed
  13. Oncogene. 2008 Sep 11;27(40):5288-302 - PubMed
  14. Curr Med Chem. 2009;16(36):4869-88 - PubMed
  15. J Chemother. 2006 Aug;18(4):415-20 - PubMed
  16. Int J Cancer. 2011 Feb 1;128(3):691-701 - PubMed
  17. Mol Biol Cell. 2008 Oct;19(10):4062-75 - PubMed
  18. Cell. 1994 Jul 15;78(1):67-74 - PubMed
  19. J Hematol Oncol. 2010 Feb 04;3:5 - PubMed
  20. Int J Oncol. 2007 Sep;31(3):633-41 - PubMed
  21. Science. 1996 Apr 19;272(5260):408-11 - PubMed
  22. Mol Cell Biol. 2005 Oct;25(19):8415-29 - PubMed
  23. Mol Carcinog. 2006 Dec;45(12):901-13 - PubMed
  24. Curr Cancer Drug Targets. 2010 Mar;10(2):210-28 - PubMed
  25. Mol Biol Cell. 2007 Nov;18(11):4615-24 - PubMed
  26. Anticancer Res. 2007 Mar-Apr;27(2):741-8 - PubMed
  27. Oncogene. 2010 Jul 8;29(27):3942-52 - PubMed
  28. Mol Carcinog. 2008 Feb;47(2):137-47 - PubMed
  29. Cancer Res. 2006 Sep 15;66(18):9245-51 - PubMed
  30. Cancer Cell Int. 2006 Jan 31;6:2 - PubMed
  31. Oncogene. 2009 Aug 20;28(33):2925-39 - PubMed
  32. Cell Prolif. 2009 Dec;42(6):711-20 - PubMed
  33. Clin Cancer Res. 2010 Apr 15;16(8):2320-32 - PubMed
  34. Neoplasia. 2006 Jun;8(6):446-57 - PubMed

Publication Types