Pioglitazone in chemically induced mammary carcinogenesis in rats

Abstract

Data available from in-vitro and in-vivo studies suggest oncostatic properties of peroral antidiabetics, thiazolidinediones, in many types of cancer. This study is the first report on the chemopreventive effect of pioglitazone in mammary carcinogenesis in rats. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea administered in two intraperitoneal doses per 50 mg/kg bodyweight on the 43rd and 50th postnatal days. Pioglitazone was administered in the diet at concentrations of 10 and 100 ppm, respectively, 12 days before the first carcinogen dose until the termination of the experiment. During the experiment, the animals were weighed weekly and palpated for the presence of mammary tumors, and the incidence, latency, tumor frequency, and tumor volume were recorded. The experiment was terminated 17 weeks after the first carcinogen dose; basic tumor growth parameters and metabolic and hormonal variables were evaluated. Pioglitazone at higher concentration decreased incidence and frequency per group from the 11th week of experiment when compared with the control group and a group receiving a lower dose. Pioglitazone at a higher dose decreased the final incidence by 38%, frequency per group by 63%, and extended latency period by 32% when compared with the control group. Our data suggest that pioglitazone and other glitazones should be further investigated for oncopreventive effects.

Metabolic Effects of Pioglitazone in Chemically-Induced Mammary Carcinogenesis in Rats

“…Thiazolidinediones inhibited mammary carcinogenesis in vivo too [7,[11][12][13]. Our group found significant tumour growth inhibition in chemically-induced mammary carcinogenesis in Sprague-Dawley rats after long-term pioglitazone administration [14].…”

Rosiglitazone Shows Partial Oncostatic Effect in Rat Mammary Carcinogenesis

“…Animal studies showed inhibition of glioma [19,20], neuroblastoma [21,22], lung [23], pancreatic [24], liver [25][26][27], colon [28], adrenocortical [29], ovarian [30,31], and melanoma cancer cells [32]. Thiazolidinedione administration inhibited mammary carcinogenesis too, which was reported by several authors including our group [33][34][35][36]. Reports on thiazolidinedione administration in cancer patients, however, are scarce.…”

“…Still, NMU+ROS10 group showed best histopathology profile with low-grade tumors prevalence, in NMU and NMU+ROS100 group high-grade/low-grade tumor ratio was balanced. The antitumor effect of the other thiazolidinedione, pioglitazone was better, in our previous work higher dose of pioglitazone (100 ppm) in the same experimental model significantly decreased tumor frequency per group (by 63%) and lengthened the latency period (by 32%) [36].…”

“…The same model was used in our previous work where we confirmed antitumor property of pioglitazone [36]. Again, we chose preventive-curative model in order to cover both initiation and promotion/progression stage of carcinogenesis.…”

Suppressive Effect of Pioglitazone, a PPAR Gamma Ligand, on Azoxymethane-induced Colon Aberrant Crypt Foci in KK-AуMice

“…Thus, pioglitazone may be a potential chemopreventive agent against colorectal carcinogenesis. Furthermore, pioglitazone may be a more useful chemopreventive agent against obesity-associated cancers, such as mammary cancer (Bojková et al, 2010).…”