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Inhibition of phorbol ester-induced mouse skin tumor promotion and COX-2 expression by celecoxib: C/EBP as a

Kyung-Soo Chun1, Joydeb Kumar Kundu, Kwang-Kyun Park

  • 1National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, Korea.

Cancer Research and Treatment
|September 23, 2009
PubMed
Abstract

Insights

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, effectively suppressed skin tumor promotion in mice. This cancer prevention was linked to reduced vascular endothelial growth factor (VEGF) and CCAAT/enhancer binding protein (C/EBP) activation.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Inflammation is a key driver of cancer development.
  • Nonsteroidal anti-inflammatory drugs, particularly cyclooxygenase-2 (COX-2) inhibitors, show promise in cancer prevention.
  • Understanding the molecular mechanisms of these drugs is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the potential of celecoxib in preventing chemically induced skin tumors in mice.
  • To elucidate the molecular pathways through which celecoxib exerts its antitumor effects.

Main Methods:

  • A two-stage mouse skin tumorigenesis model using 7,12-dimethylbenz [alpha]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA).
  • Western blot analysis to assess the expression of COX-2, vascular endothelial growth factor (VEGF), p65, and CCAAT/enhancer binding protein (C/EBP) isoforms.
  • Electrophoretic mobility gel shift assay to evaluate transcription factor DNA binding activities.

Main Results:

  • Topical celecoxib significantly reduced papilloma multiplicity in the mouse skin tumor model.
  • Celecoxib pretreatment decreased the expression of COX-2 and VEGF in papillomas.
  • Celecoxib inhibited TPA-induced DNA binding of C/EBP transcription factors and suppressed nuclear C/EBPdelta expression.

Conclusions:

  • Celecoxib demonstrates significant inhibitory effects on mouse skin tumor promotion.
  • The antitumor effects are associated with reduced COX-2 and VEGF expression.
  • Celecoxib's mechanism involves the inhibition of C/EBP activation pathways.
Keywords:
C/EBPCelecoxibChemopreventionCyclooxygenase-2Mouse skin carcinogenesisNF-κBVEGF

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