The effect of PPARgamma ligands on UV- or chemically-induced carcinogenesis in mouse skin

Guobin He1, Stephanie Muga, Philippe Thuillier

  • 1The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA.

Insights

PPARgamma ligands, like rosiglitazone and troglitazone, did not prevent skin tumors in mice. These compounds showed no significant effect on UV or chemically induced skin carcinogenesis, suggesting limited chemopreventive potential.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands are investigated for cancer chemoprevention.
  • Previous studies suggest PPARgamma's role in preventing mammary and colon tumor development.
  • Mice with reduced PPARgamma gene expression show increased susceptibility to skin carcinogenesis.

Purpose of the Study:

  • To evaluate the chemopreventive efficacy of PPARgamma ligands (rosiglitazone and troglitazone) against UV and DMBA/TPA-induced skin carcinogenesis in mice.
  • To determine the effect of these ligands on keratinocyte proliferation and PPARgamma expression in mouse skin.

Main Methods:

  • Utilized SKH-1 hairless mice subjected to UV irradiation or DMBA/TPA treatment.
  • Administered rosiglitazone and troglitazone via diet or topical application.
  • Assessed tumor development, keratinocyte proliferation (BrdU labeling), and PPARgamma expression (Northern blot analysis).

Main Results:

  • Neither rosiglitazone nor troglitazone significantly inhibited UV-induced skin tumor formation.
  • Dietary rosiglitazone did not significantly inhibit DMBA/TPA-induced skin tumors.
  • Troglitazone reduced basal keratinocyte proliferation but not TPA-induced proliferation; PPARgamma expression was minimal in normal epidermis and skin tumors.

Conclusions:

  • PPARgamma ligands (rosiglitazone, troglitazone) demonstrated no significant chemopreventive effect against UV or chemically induced skin tumors in mice.
  • The low expression of PPARgamma in mouse skin suggests it may not be a primary target for skin cancer chemoprevention.
  • Further research is needed to explore alternative therapeutic strategies for skin cancer prevention.

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