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Published on: September 30, 2016

Protein kinase Cbeta is an effective target for chemoprevention of colon cancer

Alan P Fields1, Shelly R Calcagno, Murli Krishna

  • 1Departments of Cancer Biology and Pathology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.

Cancer Research
|February 18, 2009
PubMed

Insights

Protein kinase CbetaII (PKCbetaII) drives colon cancer initiation. The PKCbetaII inhibitor enzastaurin effectively prevented colon tumor growth and progression in mice, highlighting its potential for colon cancer chemoprevention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Prevention

Background:

  • Colon cancer develops over 10-15 years, offering a window for chemoprevention.
  • Effective molecular targets for colon cancer chemoprevention are limited.
  • Protein kinase CbetaII (PKCbetaII) is crucial in colon carcinogenesis, promoting proliferation and beta-catenin accumulation.

Purpose of the Study:

  • To evaluate PKCbetaII as a target for colon cancer chemoprevention.
  • To test the efficacy of the PKCbeta-selective inhibitor enzastaurin in a mouse model of colon carcinogenesis.

Main Methods:

  • Utilized a mouse model of azoxymethane-induced colon carcinogenesis.
  • Administered enzastaurin (LY317615), a PKCbeta-selective inhibitor.
  • Assessed tumor initiation, progression, cell proliferation, beta-catenin accumulation, and gene expression.

Main Results:

  • Enzastaurin significantly reduced azoxymethane-induced colon tumor initiation and progression.
  • The drug inhibited PKCbetaII-mediated tumor cell proliferation and beta-catenin accumulation.
  • Enzastaurin decreased the expression of PKCbetaII, cyclooxygenase II, and vascular endothelial growth factor.

Conclusions:

  • PKCbetaII is a validated target for colon cancer chemoprevention.
  • Enzastaurin demonstrated efficacy in preventing colon tumor initiation and progression in a preclinical model.
  • Enzastaurin may be a promising chemopreventive agent for individuals at high risk of colon cancer.

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