Abstract

EVALUATION OF THE ANTICARCINOGENIC EFFECT OF SOME PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR LIGANDS ON DIMETHYLBENZ (α) ANTHRACENE INDUCED MAMMARY TUMOR IN FEMALE RATS

Remonda E. Rizk, Wessam F. El-Hadidy*, Malak A. Zoheir, Nesrine S. Ibrahim

Abstract

  Introduction: Breast cancer is the leading cause of cancer death amongfemales worldwide. Peroxisome proliferator activated receptors(PPARs) are one of several nuclear receptors involved in the biologyof breast cancer. Aim: Compare the effect of fenofibrate (PPARαligand), pioglitazone (PPAR γ ligand) and omega-3 (PPARα, γ ligand)and their probable mechanisms of action on 7, 12 dimethylbenz (α)anthracene (DMBA)-induced mammary carcinoma in female rats.Methods: Fifty female Waister albino rats were utilized, with tenserving as plain controls. The remaining were subjected to induction ofmammary carcinomas by oral intubation with a single dose of 20 mgDMBA suspended in one ml of sesame oil. After the appearance ofmammary tumors, rats were randomly assigned to 4 orally-treatedgroups: untreated, fenofibrate, pioglitazone and omega-3-treated for 28days. Assessed parameters: Percentage change of tumor volume, serum and tumor tissuevascular endothelial growth factor levels, tumor caspase-3 and cyclooxygenase-2concentrations, as well as immunohistochemical detection of Ki-67 expression. Results: Theuntreated rats had progressive increase in mammary tumor volume. Treatment withfenofibrate, pioglitazone or omega-3 significantly reduced the rate of tumor growth viaantiangiogenic, proapoptotic, antiproliferative and anti-inflammatory effects. Conclusion: Fenofibrate, pioglitazone and omega-3 exerted anti-tumor effects on breast cancer induced in rats via numerous mechanisms of action.

Keywords: Peroxisome proliferator activated receptors, fenofibrate, pioglitazone, omega-3, cyclooxygenase-2, induced mammary tumor.