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Updated: Apr 27, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA

Published on: December 19, 2019

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Chemopreventive effect of a novel, selective TACE inhibitor on DMBA- and TPA-induced skin carcinogenesis

Manoranjan Sharma1, Jogeswar Mohapatra, Anil Argade

  • 1Department of Pharmacology and.

Immunopharmacology and Immunotoxicology
|June 21, 2014
PubMed
Abstract

Insights

A novel TACE inhibitor, compound 11p, effectively reduced skin inflammation and suppressed tumor development in mice. This selective blockade of Tumor Necrosis Factor-alpha Converting Enzyme (TACE) shows promise for treating skin cancer by targeting inflammatory pathways.

Area of Science:

  • Dermatology
  • Oncology
  • Immunology

Background:

  • Tumor Necrosis Factor-alpha (TNF-α) is a key pro-inflammatory cytokine in cancer pathogenesis.
  • Tumor Necrosis Factor-alpha Converting Enzyme (TACE) is crucial for releasing active TNF-α.

Purpose of the Study:

  • To evaluate the efficacy of a novel, selective TACE inhibitor (compound 11p) in mitigating skin inflammation and tumorigenesis in a mouse model.
  • To investigate the anti-tumorigenic potential of inhibiting TACE in skin cancer development.

Main Methods:

  • Skin edema was induced using 12-O-tetradecanoylphorbol-13-acetate (TPA); compound 11p was applied topically for post-treatment evaluation.
  • Inflammation was assessed by measuring ear thickness, skin punch weight, and cytokine levels (TNF-α, IL-6, IFN-γ, IL-17, PGE2).
  • Skin cancer was initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted with TPA; papilloma incidence and multiplicity were assessed under compound 11p treatment.

Main Results:

  • Compound 11p significantly reduced TPA-induced skin thickness and weight, along with inflammatory cell infiltration.
  • A dose-dependent decrease in TPA-mediated pro-inflammatory cytokines and PGE2 was observed.
  • Treatment with compound 11p delayed cancer onset and markedly reduced papilloma incidence and multiplicity.

Conclusions:

  • Selective TACE inhibition effectively suppresses TPA-induced epidermal hyperplasia, inflammation, and cytokine elevation.
  • Inhibition of TACE-mediated inflammatory pathways contributes to the anti-tumorigenic effects observed in a mouse skin cancer model.
  • Compound 11p demonstrates potential as a therapeutic agent for skin inflammation and cancer by targeting TACE.
Keywords:
EGFRTNF-αTNF-α converting enzymeinflammationskin cancer

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