Rosiglitazone Shows Partial Oncostatic Effect in Rat Mammary Carcinogenesis

Abstract

Peroral antidiabetics from thiazolidinedione (glitazone) group showed oncostatic effects in preclinical models. This study evaluated chemopreventive effects of rosiglitazone in N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. N-methyl-N-nitrosourea was administered in two intraperitoneal doses each per 50 mg/kg b.w. between 40 th and 51 st postnatal days. Rosiglitazone was administered in a diet at a concentration of 10 ppm and 100 ppm, respectively, 9 days before the first carcinogen dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors and estimation of latency period, tumor frequency per group and animal, and tumor volume were recorded. The experiment was terminated 16 weeks after the first carcinogen dose, basic tumor growth parameters and selected metabolic and hormonal variables were evaluated. Chemoprevention with higher rosiglitazone dose decreased tumor frequency per group by 44%, other tumor parameters (incidence, tumor frequency per animal) were decreased insignificantly (at both doses), latency period was not changed. Rosiglitazone administration decreased cumulative tumor volume, more efficiently at lower dose. Glycaemia and insulinaemia decreased after lower rosigitazone dose administration but glycaemia did not exceed normal values. Higher rosiglitazone dose alleviated some metabolic alterations resulting from cancer progression more effectively but induced a prominent cardiac hypertrophy.

Isolated Soy Protein Promotes Mammary Tumor Development Induced by the Type I Insulin-like Growth Factor Receptor in Transgenic Mice

“…Differences between the AIN-93G-based diets (casein and ISP diets) and the Teklad 2018-based diets include the levels of vitamin A, vitamin K, several B vitamins (B1, B2, B3, B5, B6, B7, and B9) and the complexity of the carbohydrates. Vitamins B2 (riboflavin), B6 (pyridoxine), and B9 (folate) have been implicated in reducing breast cancer risk (28-30) while higher blood glucose levels associated with simple carbohydrates like those found in the casein and ISP diets have been associated with increased breast cancer risk in humans (31)(32)(33)(34) and rodents (35)(36)(37).…”

Melatonin May Increase Anticancer Potential of Pleiotropic Drugs

“…PPARγ activation is regarded as the key mechanism of anticancer effects of glitazones. PPARγ agonists, in most cases, inhibited proliferation and growth of experimental breast, lung, gastrointestinal, liver, pancreatic, ovarian, testicular and urinary system cancers [292,293,294,295,296]. Antitumor properties independent of PPARγ activation were reported too, including the regulation of differentiation, inflammation and apoptosis; however, it is not always possible to determine whether an effect that is independent of PPARγ-regulated transcriptional control is also independent of the presence of PPARγ protein [297,298].…”

Research Advances in the Correlation between Peroxisome Proliferator-Activated Receptor-γ and Digestive Cancers

“…It is involved in the regulation of carbohydrate metabolism and adipogenesis in cells and also participates in the inflammatory response as well as the differentiation and apoptosis of tumor cells [ 15 ]. Researchers has found that after being activated by ligand, PPAR γ can induce tumor cell differentiation, repress their proliferation, promote their apoptosis, and concomitantly reduce neoplastic angiogenesis, which eventually halts the tumor growth, proliferation, infiltration, and metastasis [ 16 , 17 ]. Its most important function is mediation of gene transcription and subsequent regulation on its activation after combining with its ligands.…”