Therapeutic treatment of DMBA-induced mammary tumors with PPAR ligands

G M Pighetti1, W Novosad, C Nicholson

  • 1Department of Dairy and Animal Science, University of Tennessee, 114B McCord, 2640 Morgan Circle Drive, Knoxville, TN 37996, USA. gpighetti@utk.edu

Anticancer Research
|June 9, 2001
PubMed

Insights

Wy-14,643 and troglitazone, PPAR ligands, slowed mammary tumor growth in rats. Wy-14,643 also reduced malignant tumor development, showing promise in cancer research.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Mammary tumors are a significant health concern.
  • 7,12-dimethylbenz(a)anthracene (DMBA) is a known carcinogen used to induce mammary tumors in research models.
  • Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in various metabolic processes and have been implicated in cancer development.

Purpose of the Study:

  • To evaluate the efficacy of troglitazone (a thiazolidinedione) and Wy-14,643 (a clofibrate), both PPAR ligands, in inhibiting the progression of DMBA-induced mammary tumors in rats.
  • To compare the effects of these PPAR ligands with no treatment and tamoxifen, a standard breast cancer treatment.

Main Methods:

  • Rats were induced with DMBA to develop mammary tumors.
  • Tumor progression was monitored in groups treated with troglitazone, Wy-14,643, tamoxifen, or no treatment.
  • Tumor incidence, malignancy, regression, stasis, and additional tumor development were assessed.

Main Results:

  • Wy-14,643 reduced the incidence of malignant tumors compared to troglitazone and controls.
  • Both Wy-14,643 and troglitazone induced regression or stasis of tumor volume in 40-50% of animals with detectable tumors, outperforming controls (10%) but less than tamoxifen (65%).
  • Both PPAR ligands were effective in preventing additional tumor development, similar to tamoxifen.

Conclusions:

  • PPAR ligands, particularly Wy-14,643, show potential in managing mammary tumor progression.
  • Wy-14,643, a PPAR-alpha activator, demonstrated a unique ability to reduce malignant tumor development when administered early.
  • These findings suggest PPAR ligands could be a valuable therapeutic strategy in oncology, warranting further investigation.

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