The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

Changes in miR-124-1, miR-212, miR-132, miR-134, and miR-155 Expression Patterns after 7,12-Dimethylbenz(a)anthracene Treatment in CBA/Ca Mice.

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents.

Effects of cytochrome P450 1A1 and uridine-diphosphate-glucuronosyltransferase 1A1 allelic polymorphisms on the risk of development and the prognosis of head and neck cancers.

We studied the effect of allelic polymorphisms of cytochrome P450 1A1 (CYP1A1) and uridine-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) on the risk of development of head and neck cancers and overall survival. One hundred and forty-two head and neck cancer patients (48 with laryngeal, 42 with hypopharyngeal and 52 with mesopharyngeal tumours) were included in the study. The control group (150 individuals) included volunteers without malignant tumours. There was no statistically significant difference in age, sex distribution, or smoking habits between the two groups. The participants were genotyped for the CYP1A1 isoleucine/valine (Ile/Val) polymorphism in exon 7 and for the UGT1A1 thymine-adenine-repeat polymorphism (*1 and *28 alleles) in the promoter region of the gene. The effect of the allelic variants on survival was studied using the log-rank test, whereas the χ-test and odds ratios (OR) with 95% confidence intervals (CI) were used to compare the allelic frequencies between patients and controls. Our study revealed a significant link between the occurrence of the CYP1A1 Ile/Val, Val/Val (OR: 1.72, 95% CI: 1.02-2.96, P=0.044) and UGT1A1*28 alleles (OR: 2.74, 95% CI: 1.45-5.18, P=0.002) and an increased risk of head and neck cancers. These alleles decreased the duration of survival significantly (P=0.018 and 0.006). The survival was significantly more strongly reduced when the two high-risk alleles were carried simultaneously (OR: 2.149, 95% CI: 1.111-4.157, P=0.001). Our results suggest that the use of the CYP1A1 Ile/Val and Val/Val variants and UGT1A1*28 as biomarkers can aid risk assessment while their prognostic value can aid planning of individual therapy.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

The effect of aspartame administration on oncogene and suppressor gene expressions.

BACKGROUND: Aspartame (L-phenylalanine N-L-alpha-aspartyl-1-methyl ester) is an artificial sweetener with widespread applications. Previously published results have shown that among rats receiving aspartame a significant increase of lymphoreticular neoplasms, brain tumours and transitional cell tumours occurred. The aim of our short-term experiment was to investigate the biological effect of aspartame consumption by determining the expressions of key oncogenes and a tumour suppressor gene. MATERIALS AND METHODS: After one week per os administration of various doses of aspartame to CBA/CA female mice, p53, c-myc, Ha-ras gene expression alterations were determined in individual organs. RESULTS: The results showed an increase in gene expressions concerning all the investigated genes especially in organs with a high proliferation rate: lymphoreticular organs, bone-marrow and kidney. CONCLUSION: Aspartame has a biological effect even at the recommended daily maximum dose.