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Chlorogenic acid (CA), also known as 5- O -caffeoylquinic acid, is a dietary phenolic acid produced by various plant species. CA, is the most ubiquitous compound among the phenolic acid group, is also present in tea and green coffee extracts. Its consumption reduces the risk of numerous diseases as validated by preclinical and clinical studies. CA possesses a wide range of pharmacological properties, such as hepatoprotective, antimicrobial, immunomodulatory, antioxidant, antidiabetic, and anticancer activities. It has been extensively used in the food, chemical, medicine, and health care industries. Available reports revealed that CA can exert anticancer activity by inhibiting the cell cycle, triggering apoptosis, and suppressing the proliferation of cancer cells. It upregulates the expression of nuclear factor of activated T cells 2 (NFATC2) and NFATC3 genes involved in immune pathway and downregulates B cell-specific moloney murine leukemia virus integration site 1 protein and SRY-box transcription factor 2 gene expression to facilitate tumor cell destruction. It promotes intracellular DNA impairment and topoisomerase I- and topoisomerase-II-DNA complex formation that perform a key function in apoptosis. In addition, CA has been documented to be an effective natural anticancer drug and was approved by the China Food and Drug Administration. Several previously published reports have provided fragmented summary of various anticancer activities of CA. Therefore, this review aims to deliver up-to-date and comprehensive assessment about the natural sources of CA, its bioavailability, metabolism, and anticancer property with an emphasis on the molecular mechanisms associated with several signaling pathways in tumor cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Dithiocarbamates (DTCs), important therapeutic and industrial chemicals released in high quantities into the environment, exhibit complex chemical and biological activities. Here, we demonstrate an effect of DTCs on glucocorticoid action due to inhibition of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2, converting cortisol to cortisone in the kidney, but not 11β-HSD1, catalyzing the reverse reaction in liver and adipose tissue. Thus, DTCs may locally increase active glucocorticoid concentrations. Preincubation with the DTC thiram abolished 11β-HSD2 activity, suggesting irreversible enzyme inhibition. The sulfhydryl protecting reagent dithiothreitol blocked thiram-induced inhibition and NAD+ partially protected 11β-HSD2 activity, indicating that DTCs act at the cofactor-binding site. A 3D-model of 11β-HSD2 identified Cys90 in the NAD+-binding site as a likely target of DTCs, which was supported by a 99% reduced activity of mutant Cys90 to serine. The interference of DTCs with glucocorticoid-mediated responses suggests a cautious approach in the use of DTCs in therapeutic applications and in exposure to sources of DTCs such as cosmetics and agricultural products by pregnant women and others. [Copyright &y& Elsevier]

We review the microarray studies of resveratrol in several experimental models of CVDs and cardiovascular risk factors. Microarrays were used to detect expression changes induced by resveratrol in cell cultures or tissue samples. Microarray analyses were followed by bioinformatics aiming at the identification of differentially expressed genes or biological pathways. Resveratrol, a phytoalexin, is a natural polyphenol synthesized exclusively by plants in response to environmental stresses. However, the molecule has also many exogenous bioactivities in animal cells. These bioactivities may lead to anti-cancer and cardio-protective health benefits. Because cellular responses to the treatment with resveratrol include the changes of expression patterns, functional genomics is an attractive tool to study them. In recent and today's experimental practice, this mostly means microarray profiling of gene expression (using RNAs isolated from bulk tissues). Herein, we review such published studies undertaken in the context of cardiovascular diseases (CVDs). CVDs are a number one public health problem in developed countries, outweighing in magnitude even cancer. In particular, we review the studies of resveratrol in several animal models relevant to CVDs. These models included: normal and pre-mature aging in mice, as well as atherogenic diet in mice / pigs / non-human primates. Additionally, there were few clinical studies published in the context of the comorbidities of atherosclerosis in humans (e.g. obesity, diabetes, hypertension). For the purposes of these studies, three types of samples were most commonly profiled with microarrays: the liver, the skeletal muscle, and peripheral blood mononuclear cells. Resveratrol-induced changes of gene expression typically mimicked those associated with calorie restriction and lifespan extension. They also opposed changes induced by the atherogenic diet. We conclude by discussing few experimental factors that were relatively neglected thus far, but which could be interesting to investigate in the future. These factors include sex and the exact formulation of resveratrol (plant extract, or synthetic chemical). [ABSTRACT FROM AUTHOR]

Curcumin is a natural plant-derived compound that has attracted a lot of attention for its anti-cancer activities. Curcumin can slow proliferation of and induce apoptosis in cancer cell lines, but the precise mechanisms of these effects are not fully understood. However, many lines of evidence suggested that curcumin has a potent impact on gene expression profiles; thus, functional genomics should be the key to understanding how curcumin exerts its anti-cancer activities. Here, we review the published functional genomic studies of curcumin focusing on cancer. Typically, a cancer cell line or a grafted tumor were exposed to curcumin and profiled with microarrays, methylation assays, or RNA-seq. Crucially, these studies are in agreement that curcumin has a powerful effect on gene expression. In the majority of the studies, among differentially expressed genes we found genes involved in cell signaling, apoptosis, and the control of cell cycle. Curcumin can also induce specific methylation changes, and is a powerful regulator of the expression of microRNAs which control oncogenesis. We also reflect on how the broader technological progress in transcriptomics has been reflected on the field of curcumin. We conclude by discussing the areas where more functional genomic studies are highly desirable. Integrated OMICS approaches will clearly be the key to understanding curcumin’s anticancer and chemopreventive effects. Such strategies may become a template for elucidating the mode of action of other natural products; many natural products have pleiotropic effects that are well suited for a systems-level analysis. [ABSTRACT FROM AUTHOR]

Microbial polysaccharides (MPs) offer immense diversity in structural and functional properties. They are extensively used in advance biomedical science owing to their superior biodegradability, hemocompatibility, and capability to imitate the natural extracellular matrix microenvironment. Ease in tailoring, inherent bio-activity, distinct mucoadhesiveness, ability to absorb hydrophobic drugs, and plentiful availability of MPs make them prolific green biomaterials to overcome the significant constraints of cancer chemotherapeutics. Many studies have demonstrated their application to obstruct tumor development and extend survival through immune activation, apoptosis induction, and cell cycle arrest by MPs. Synoptic investigations of MPs are compulsory to decode applied basics in recent inclinations towards cancer regimens. The current review focuses on the anticancer properties of commercially available and newly explored MPs, and outlines their direct and indirect mode of action. The review also highlights cutting-edge MPs-based drug delivery systems to augment the specificity and efficiency of available chemotherapeutics, as well as their emerging role in theranostics. [ABSTRACT FROM AUTHOR]

Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. [ABSTRACT FROM AUTHOR]

Nutrigenomics effects have an important role in the manipulation of dietary components for human benefit, particularly in cancer prevention or treatment. The impact of dietary components, including phytochemicals, is largely studied by nutrigenomics, looking at the gene expression and molecular mechanisms interacting with bioactive compounds and nutrients, based on new ‘omics’ technologies. The high number of preclinical studies proves the relevant role of nutrigenomics in cancer management. By deciphering the network of nutrient-gene connections associated with cancer, relevant data will be transposed as therapeutic interventions for this devastating pathology and for fulfilling the concept of personalized nutrition. All these are presented under the nutrigenomics canopy for a better comprehension of the relation between ingested phytochemicals and chemoprevention or chemotherapy. The profits from the nutrigenomics progress, with a particular focus on the coding and noncoding genes related to the exposure of natural compounds need to be validated. A precise attention receives the evaluation of the role of natural compounds in tandem with conventional therapy using genomic approaches, with emphasis on the capacity to inhibit drug resistance mechanisms. All these relevant nutrigenomics aspects are summarized in the present review paper. It is concluded that further nutrigenomics studies are required to improve our understanding related to the complex mechanisms of action of the natural compounds and for their appropriate application as gears in cancer therapy. [ABSTRACT FROM AUTHOR]

The nutraceutical market is currently a high-impact multi-billion-dollar industry, and it is anticipated to grow rapidly over the next decade. Nutraceuticals comprise diverse food-derived product categories that have become widespread due to increased consumer awareness of potential health benefits and the need for improved wellness. This targeted review is designed to identify the current global trends, market opportunities, and regulations that drive the nutraceutical industry. Safety and efficacy concerns are also explored with a view to highlighting areas that necessitate further research and oversight. Key drivers of the nutraceutical market include aging populations, consumer awareness, consumer lifestyle, increasing cost of healthcare, and marketing channels. Although some nutraceuticals hold promising preventive and therapeutic opportunities, there is a lack of a universal definition and regulatory framework among countries. Moreover, there is a lack of adequate evidence for their efficacy, safety, and effectiveness, which was even further highlighted during the ongoing coronavirus pandemic. Future prospective epidemiological studies can delineate the health impact of nutraceuticals and help set the scientific basis and rationale foundation for clinical trials, reducing the time and cost of trials themselves. Together, an understanding of the key drivers of the nutraceutical market alongside a consistent and well-defined regulatory framework will provide further opportunities for growth, expansion, and segmentation of nutraceuticals applications. [Display omitted] [ABSTRACT FROM AUTHOR]