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.

• 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

Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

• Keywords
• angiogenesis, breast cancer, galectins, genistein, soy,
• MeSH
• Genistein chemistry   pharmacology   therapeutic use   MeSH
• Glycine max chemistry   MeSH
• Angiogenesis Inhibitors chemistry   pharmacology   therapeutic use   MeSH
• Isoflavones chemistry   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Breast Neoplasms blood supply   drug therapy   metabolism   pathology   MeSH
• Neovascularization, Pathologic drug therapy   metabolism   pathology   MeSH
• Breast blood supply   drug effects   metabolism   pathology   MeSH
• Signal Transduction drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Genistein MeSH
• Angiogenesis Inhibitors MeSH
• Isoflavones MeSH