Nutrigenomics

Dietary cancer-chemopreventive compounds: from signaling and gene expression to pharmacological effects

Chen, C & Kong, A N T, 2005. Trends in Pharmacol. Sci. 26(6):318-326

Abstract

The process of cancer development (carcinogenesis leading to advanced metastasized cancers) in humans generally takes many years through initiation, promotion and progression. Because advanced metastasized cancers are almost impossible to treat, cancer chemoprevention for the control and containment of early cancer development is highly desirable. Recent studies have provided strong evidence that many daily-consumed dietary compounds possess cancer-protective properties that might interrupt the carcinogenesis process. These properties include the induction of cellular defense detoxifying and antioxidant enzymes, which can protect against cellular damage caused by environmental carcinogens or endogenously generated reactive oxygen species. These compounds can also affect cell-death signaling pathways, which could prevent the proliferation of tumor cells. In this review, we will summarize current knowledge on dietary cancer-chemopreventive compounds and their induction of detoxifying enzymes and anti-proliferative effects, and discuss the challenges in translating these signaling and gene-expression events to pharmacological effects.

Journal Link | PMID

Comments

A well illustrated review demonstrating the important relationship between diet and disease, with its focus on cancer.  This review ties together the various expanding fields of genomics and the growing information in nutriceuticals.

The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis.

Fenech, M, 2005. Mutagenesis 20(4):255-269.

The evidence of a direct link between increased genome/epigenome damage and elevated risk for adverse health outcomes during the various stages of life, such as infertility, foetal development and cancer is becoming increasingly stronger. The latter is briefly reviewed against a background of evidence indicating that genome and epigenome damage biomarkers, in the absence of overt exposure of genotoxins, are themselves sensitive indicators of deficiency in micronutrients required as cofactors or as components of DNA repair enzymes, for maintenance methylation of CpG sequences and prevention of DNA oxidation and/or uracil incorporation into DNA. The latter is illustrated with cross-sectional and dietary intervention data obtained using the micronucleus assay and other efficient biomarkers for diagnosing genome and/or epigenome instability. The concept of recommended dietary allowances for genome stability and how this could be achieved is discussed. The 'Genome Health Nutrigenomics' concept is also introduced to define and focus attention on the specialized research area of how diet impacts on genome stability and how genotype determines nutritional requirements for genome health maintenance. The review concludes with a vision for a paradigm shift in disease prevention strategy based on the diagnosis and nutritional treatment of genome/epigenome damage on an individual basis, i.e. The Genome Health Clinic.

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Kaput, J. et al. 2005. Br. J. Nutrition 94(5):623-632

Abstract:

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

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Comment

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Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression

Kijima I et al., 2006. Cancer Res. 66(11):5960-5967

Abstract

Aromatase is the enzyme that converts androgen to estrogen. It is expressed at higher levels in breast cancer tissues than normal breast tissues. Grape seed extract (GSE) contains high levels of procyanidin dimers that have been shown in our laboratory to be potent inhibitors of aromatase. In this study, GSE was found to inhibit aromatase activity in a dose-dependent manner and reduce androgen-dependent tumor growth in an aromatase-transfected MCF-7 (MCF-7aro) breast cancer xenograft model, agreeing with our previous findings. We have also examined the effect of GSE on aromatase expression. Reverse transcription-PCR experiments showed that treatment with 60 mug/mL of GSE suppressed the levels of exon I.3-, exon PII-, and exon I.6-containing aromatase mRNAs in MCF-7 and SK-BR-3 cells. The levels of exon I.1-containing mRNA, however, did not change with GSE treatment. Transient transfection experiments with luciferase-aromatase promoter I.3/II or I.4 reporter vectors showed the suppression of the promoter activity in a dose-dependent manner. The GSE treatment also led to the down-regulation of two transcription factors, cyclic AMP-responsive element binding protein-1 (CREB-1) and glucocorticoid receptor (GR). CREB-1 and GR are known to up-regulate aromatase gene expression through promoters I.3/II and I.4, respectively. We believe that these results are exciting in that they show GSE to be potentially useful in the prevention/treatment of hormone-dependent breast cancer through the inhibition of aromatase activity as well as its expression.

Journal Link | PMID

Comments

This research article describes molecular studies revealing how the phytochemicals in grape seeds reduce estrogen levels in hormone-dependent breast cancer cells via effects at the transcription and post-transcriptional levels.

Nutritional genomics

Ordovas, JM & Corella, D, 2004.  Ann. Rev. Genomics Hum. Genet. 5:71-118

Abstract

Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal recommendations. Nutrigenetics will provide the basis for personalized dietary recommendations based on the individual's genetic make up. This approach has been used for decades for certain monogenic diseases; however, the challenge is to implement a similar concept for common multifactorial disorders and to develop tools to detect genetic predisposition and to prevent common disorders decades before their manifestation. The preliminary results involving gene-diet interactions for cardiovascular diseases and cancer are promising, but mostly inconclusive. Success in this area will require the integration of different disciplines and investigators working on large population studies designed to adequately investigate gene-environment interactions. Despite the current difficulties, preliminary evidence strongly suggests that the concept should work and that we will be able to harness the information contained in our genomes to achieve successful aging using behavioral changes; nutrition will be the cornerstone of this endeavor.

Journal Link | PMID

Comment

This is an extensive review of nutritional aspects of disease and the role one's genetics plays in the metabolism of nutrients.  The types of experimental approaches and their applications are well described.  It also has a good glossary of the terminology in nutritional genomics/nutrigenomics.  A good reference if you want a thorough introduction to this topic.