Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25930965
DOI
10.1007/s00394-015-0910-5
PII: 10.1007/s00394-015-0910-5
Knihovny.cz E-resources
- Keywords
- Angiogenesis, Apoptosis, Cell proliferation, Fruit polyphenols, MCF-7, Mammary carcinogenesis, Rat,
- MeSH
- Ki-67 Antigen genetics metabolism MeSH
- Apoptosis drug effects MeSH
- Mammary Neoplasms, Experimental drug therapy MeSH
- Flavonoids analysis pharmacology MeSH
- DNA Fragmentation drug effects MeSH
- Antineoplastic Agents, Phytogenic analysis pharmacology MeSH
- Caspase 3 genetics metabolism MeSH
- Rats MeSH
- Humans MeSH
- Methylnitrosourea toxicity MeSH
- MCF-7 Cells MeSH
- Disease Models, Animal MeSH
- Fruit chemistry MeSH
- Polyphenols analysis pharmacology MeSH
- Cell Proliferation drug effects MeSH
- bcl-2-Associated X Protein genetics metabolism MeSH
- Vascular Endothelial Growth Factor Receptor-2 genetics metabolism MeSH
- Stilbenes analysis pharmacology MeSH
- Tyrosine analogs & derivatives metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3-nitrotyrosine MeSH Browser
- Ki-67 Antigen MeSH
- Bax protein, rat MeSH Browser
- Casp3 protein, rat MeSH Browser
- Flavin7 MeSH Browser
- Flavonoids MeSH
- Antineoplastic Agents, Phytogenic MeSH
- Caspase 3 MeSH
- Kdr protein, rat MeSH Browser
- Methylnitrosourea MeSH
- Polyphenols MeSH
- bcl-2-Associated X Protein MeSH
- Vascular Endothelial Growth Factor Receptor-2 MeSH
- Stilbenes MeSH
- Tyrosine MeSH
PURPOSE: Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. METHODS: Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed. RESULTS: High-dose F7 suppressed tumour frequency by 58 % (P < 0.001), tumour incidence by 24 % (P < 0.05), and lengthened latency by 8 days (P > 0.05) in comparison with the control rats, whereas lower dose of F7 was less effective. Histopathological analysis of tumours showed significant decrease in the ratio of high-/low-grade carcinomas after high-dose F7 treatment. Immunohistochemical analysis of rat carcinoma cells in vivo found a significant increase in caspase-3 expression and significant decrease in Bcl-2, Ki67, and VEGFR-2 expression in the high-dose group. Both doses demonstrated significant positive effects on plasma lipid metabolism in rats. F7 significantly decreased survival of MCF-7 cells in vitro in MTT assay by dose- and time-dependent manner compared to control. F7 prevented cell cycle progression by significant enrichment in G1 cell populations. Incubation with F7 showed significant increase in the percentage of annexin V-/PI-positive MCF-7 cells and DNA fragmentation. CONCLUSIONS: Our results reveal a substantial tumour-suppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.
Department of Anatomy Comenius University Martin Slovakia
Department of Histology and Embryology Comenius University Martin Slovakia
Department of Medical Biochemistry Comenius University Martin Slovakia
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