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Upregulation of GADD153 by butyrate: involvement of MAPK

David W Scott1, Jennifer M Longpre, George Loo

  • 1Department of Nutrition, Cellular and Molecular Nutrition Research Laboratory, University of North Carolina at Greensboro, Greensboro, North Carolina 27402-6170, USA.

DNA and Cell Biology
|September 5, 2008
PubMed

Insights

Butyrate, a compound that inhibits cancer cell growth, upregulates the GADD153 gene via the MEK/ERK pathway. This occurs before signs of apoptosis and without causing DNA damage.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Butyrate is known to inhibit cancer cell proliferation.
  • The early molecular mechanisms underlying butyrate's effects are not fully understood.

Purpose of the Study:

  • To investigate the early molecular events triggered by butyrate in colon cancer cells.
  • To elucidate the role of GADD153 and the MAPK pathway in butyrate's action.

Main Methods:

  • Treatment of HCT-116 cells with butyrate.
  • Analysis of GADD153 gene expression using mRNA levels.
  • Inhibition of specific signaling pathways (MAPK, MEK) using chemical inhibitors.
  • Assessment of DNA damage and apoptotic markers.

Main Results:

  • Butyrate upregulated GADD153 expression in HCT-116 cells prior to apoptosis.
  • This upregulation occurred independently of detectable DNA damage.
  • The MEK/ERK pathway, but not JNK or p38, was involved in mediating butyrate's effect on GADD153 mRNA.
  • Actinomycin D attenuated GADD153 mRNA upregulation, suggesting transcriptional regulation.

Conclusions:

  • Butyrate induces GADD153 gene activation at the transcriptional level.
  • The MEK/ERK signaling pathway plays a key role in this process.
  • These events precede the manifestation of apoptosis and are not initiated by DNA damage.

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