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Abstract: There is growing interest in the diverse signaling pathways that regulate and affect breast tumorigenesis, including the role of phytochemicals and the emerging role of microRNAs (miRNAs). Recent studies demonstrate that miRNAs regulate fundamental cellular and developmental processes at the transcriptional and translational level under normal and disease conditions. While there is growing evidence to support the role of phytoalexin-mediated miRNA regulation of cancer, few reports address this role in breast cancer. Recent reports by our group and others demonstrate that natural products, including stilbenes, curcumin, and glyceollins, could alter the expression of specific miRNAs, which may lead to increased sensitivity of cancer cells to conventional anti-cancer agents and, therefore, hormone-dependent and hormone-independent tumor growth inhibition. This review will discuss how dietary intake of natural products, by regulating specific miRNAs, contribute to the prevention and treatment of breast cancer.
Key words: Phytoalexins, microRNA, breast cancer, estrogen.
Phytoalexins consist of a class of low molecular weight compounds that accumulate in plants in response to biological stress including wounding, freezing, pathogens, UV light, and exposure to agricultural chemicals. They are thought to be involved in providing plants with resistance to microbial invasion and colonization. Phytoalexins have been identified in at least 75 plant species including alfalfa, blueberries, celery, eggplant, garlic, grapes, peanuts, pepper, potato, rice, soybeans and tomatoes. Preclinical data suggest phytoalexins modulate cellular processes that impinge on cancer including proliferation, apoptosis, invasion and metastasis, hormonal regulation, and expression/ activity of Phase I and II metabolizing enzymes. Phytoalexins have also been demon- strated to target signal transduction pathways,1 nuclear receptors,2 4 apoptosis, and cell cycle pathways.5,6 While multiple epidemiological and animal studies have shown that consumption of foods rich in fruits and vegetables decreased the occurrence of cancers,710 a better understanding of the molecular mechanisms by which phytoalexins regulate these processes is critical towards an improved understanding of their potential use as preventative and/or adjunctive agents in the clinical setting.
A specific class of endogenous, non-coding RNAs, classified as microRNAs (miR- NAs), has been identified. It has been found that most miRNAs are conserved across species,11 indicating that they participate in normal biological processes. They are single-stranded RNAs of 21-25 nucleotides in length12 and found to regulate mRNA stability and translation by targeting the 3...