Induction of differentiation of colon cancer cells by combined inhibition of kinases and histone deacetylase

Michael A. Lea, Chinwe Ibeh, Neel Shah, Mary P. Moyer

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The MAP kinase pathway inhibitor U0126 in combination with butyrate promotes differentiation in some colon cancer cell lines. We examined several inhibitors of histone deacetylase (HDAC) in combination with U0126 and other protein kinase inhibitors to see if these effects are general properties of HDAC inhibitors or butyrate alone. Alkaline phosphatase and peptidase activities were examined as markers for cellular differentiation in the human colon cancer cell lines Caco-2 and HT29 and the minimally transformed NCM460. Several HDAC inhibitors caused greater increases of alkaline phosphatase in the cancer cells than in NCM460, in which butyrate was the only HDAC inhibitor that caused a consistent increase. Unlike the JNK and PKC inhibitors examined, the MEK 1/2 inhibitor U0126 induced alkaline phosphatase activity in Caco-2 as a single agent and caused additive effects with HDAC inhibitors. The PI-3 kinase inhibitor LY294002 had little effect alone but enhanced the response of most HDAC inhibitors as did the raf inhibitor GW5074. In addition to butyrate, several HDAC inhibitors can induce differentiation in colon cancer cells and the responses may be enhanced by U0126, GW5074 and LY294002.

Original languageEnglish (US)
Pages (from-to)741-748
Number of pages8
JournalAnticancer Research
Volume27
Issue number2
StatePublished - Mar 1 2007

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Histone Deacetylase Inhibitors
Histone Deacetylases
Colonic Neoplasms
Phosphotransferases
Butyrates
Alkaline Phosphatase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cell Line
Differentiation Antigens
Mitogen-Activated Protein Kinase Kinases
Protein Kinase Inhibitors
Phosphatidylinositol 3-Kinases
U 0126

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Colon cancer
  • Differentiation
  • Histone acetylation
  • Kinase inhibitors

Cite this

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Induction of differentiation of colon cancer cells by combined inhibition of kinases and histone deacetylase. / Lea, Michael A.; Ibeh, Chinwe; Shah, Neel; Moyer, Mary P.

In: Anticancer Research, Vol. 27, No. 2, 01.03.2007, p. 741-748.

Research output: Contribution to journalArticle

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