Dear Colleagues,

Chronic degenerative diseases continue to increase around the world, despite increased nutrition awareness. Obesity and type II diabetes have reached epidemic proportions in some countries. Despite increasing survival rates, cancer continues to be a social malady and an economic burden. Cancer impacts/has impacted most families in one way or another, and is a tremendous burden on the patient, the family, and society. The increase in cancer is being correlated with alterations in the environment, food habits, and lifestyles. The adoption of a healthy lifestyle can reduce the incidences of cancer development. Cancer has been claimed to be a preventable disease, as ~90% of cancer cases have a lifestyle or environmental related cause for origin, while only 5%–10% have impaired genetics as a causative factor. A diet enriched in fruits, vegetables, and their processed products is known to reduce the incidences of chronic diseases affecting several sites. Similarly, cardiovascular and cerebrovascular diseases can be prevented through an appropriate diet and lifestyle. Diet is a major source for several essential molecules that act in conjunction with antioxidant enzymes, providing protection from deleterious reactive oxygen species (ROS). Examples of these bioactives include vitamins, such as C, E; carotenoids, such as b-carotene (a precursor for vitamin A), lycopene, and xanthophylls; polyphenols (flavonoids, such as quercetin, catechin, naringenin, and anthocyanins, which include sugar derivatives of cyanidin, pelargonidin, petunidin, peonidin, and malvidin); and essential minerals, such as selenium and zinc (that act as cofactors for essential host pathway enzymes). However, a detailed understanding on the mechanism of action of nutraceuticals leading to disease prevention is needed.

Inflammation is being recognized as the initiation point for several forms of cancer and chronic diseases. Diet- and lifestyle-related risk factors, such as obesity, smoking, environmental pollutants, alcohol, irradiation, and a high fat diet, are known to be risk factors for cancer. A major link between risk factors and cancer is inflammation. The activation of major inflammatory pathways involving Nf-kB (nuclear factor kappa B), STAT3, etc., is associated with most cancers. In addition to the modulation of inflammation-related cytokine signaling and gene expression, nutraceuticals act through epigenetic mechanisms, including inhibition of histone deacetylases, micro RNAs, and the modulation of the CpG methylation of genes related to cancer development. MicroRNAs have become particularly attractive in oncology, as they are simple, stable molecules that are easy to detect in tissues and blood circulation. Increasing evidence suggests that miRNAs are involved in broad genomic processes, including the regulation of the expression of oncogenic and tumor-suppressive genes. As they are widely deregulated in cancer, miRNAs are therapeutic targets and promising diagnostic and prognostic markers of cellular growth, apoptosis, and inflammation. The greatest potential for miRNAs is their use as minimally invasive circulating biomarkers, alone or in combination with other molecules, promising to significantly improve the diagnostic and prognostic accuracy of cancer treatments and prevention. Inflammatory genes and miRNAs have causative roles in carcinogenesis, and together, they are ideal candidates as therapeutic and prevention targets. Plant polyphenols may deliver positive effects on health by regulating specific miRNA expression. The mechanism of regulation of selective miRNAs by polyphenols needs to be explored further. The up-regulation of miR-22 expression by curcumin suppresses the expression of the miR-22 target genes Sp1 and estrogen receptor 1 in human pancreatic cancer cells. Curcumin also reduces the miR-21 promoter activity and expression in primary colon cancer. Epigallocatechin gallate (EGCG) is a major green tea polyphenol that acts on cancer miR-16 to mediate apoptotic effects. Resveratrol modulates the levels of multiple miRNAs targeting genes of the TGFβ signaling pathway in SW480 colon cancer cells.

Polyphenols in the diet act in multiple ways, which include direct antioxidant action to scavenge cancer initiating free radicals, activation of the transcription of cytoprotective enzymes involved in the detoxification of xenobiotics, and the modulation of signal transduction systems. Antioxidants can activate the Keap1/Nrf2/ARE (Kelch ECH associating protein 1 /NF-E2-related factor 2/antioxidant response elements) pathway, resulting in an increased expression of phase 2 detoxification enzymes and antioxidant enzymes. Sulphoraphane in broccoli causes cytotoxicity and G2/M arrest in HT-29 colon cancer cells and MCF-7 breast cancer cells. The induction of apoptosis in cancer cells by sulphoraphane involves the activation of Bcl2 proteins Bax and Bak. Sulphoraphane causes inhibition of tubulin polymerization, activation of G2/M kinases and histone deacetylation resulting in cell cycle arrest and apoptosis. These mechanisms may enable sulphoraphane to inhibit carcinogenesis even after initiation. Thus, dietary antioxidants are compelling candidates for use as nutraceuticals in order to enhance the function of the antioxidant defense system during normal living conditions, thus preventing inflammation and decreasing the chances of developing chronic diseases.

Dr. Cristina Martínez-Villaluenga
Dr. Blanca Hernández-Ledesma
Guest Editors

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• inflammation
• chronic diseases
• diet and lifestyle
• nutraceuticals and function