Probiotic metabolites as epigenetic targets in the prevention of colon cancer

Department of Microbiology and Immunology, National Institute of Nutrition, Hyderabad, India.
Nutrition Reviews (Impact Factor: 5.54). 01/2013; 71(1):23-34. DOI: 10.1111/j.1753-4887.2012.00542.x
Source: PubMed

ABSTRACT Dietary interventions for preventing colon cancer have recently attracted increased attention from researchers and clinicians. The probiotics have emerged as potential therapeutic agents but are also regarded as healthy dietary supplements for nutrition and health applications. The probiotic metabolome may interfere with various cellular and molecular processes, including the onset and progression of colon cancer. Probiotic metabolites may lead to the modulation of diverse cellular signal transduction and metabolic pathways. The gut microbial metabolites (organic acids, bacteriocins, peptides, etc.) have been noted to interact with multiple key targets in various metabolic pathways that regulate cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis, and metastasis. Progress in this field suggests that epigenetic alterations will be widely used in the near future to manage colon cancer. The present review provides insights into the molecular basis of the therapeutic applications and the chemopreventive activities of certain probiotic metabolites, with emphasis on the interaction between these metabolites and the molecular signaling cascades that are considered to be epigenetic targets in preventing colon cancer.

Download full-text


Available from: Manoj Kumar, Oct 02, 2014
  • Source
    • "Although environmental factors such as diet are widely believed to affect the development and progression of these pathologies, exploration of the link between nutrition and angiogenesis has largely been confined to correlative studies. These include descriptions of the effects of gestational nutrition on the placental vasculature (Belkacemi et al., 2010; Rutland et al., 2007) or the pro/antiangiogenic actions of nutrients and metabolites with a potential modulatory role in cancer (Adolphe et al., 2010; Kumar et al., 2013). A tantalizing new study has shown that increasing adipose tissue vascularization can ameliorate the deleterious metabolic effects of a high-fat diet, pointing to a central metabolic role for these vascular changes (Sung et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives-rather than responds to-metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture.
    Cell 01/2014; 156(1-2):69-83. DOI:10.1016/j.cell.2013.12.008 · 33.12 Impact Factor
  • Source
    • "The probiotic metabolome has significant effects on the molecular and cellular processes leading to cancer development [Kumar et al., 2010, 2012]. The gut microbiota secretes metabolites including organic acids, baceriocins, peptides, and others, which influence aspects of cell differentiation, programmed cell death, cell proliferation, angiogenesis and cancer development [Kumar et al., 2013]. Probiotic organisms also have the capability to transform toxic compounds in the gut [Cho et al., 2009]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The microbiome is a collection of all microbial species that coexist with an individual. These organisms influence several aspects of individual body functions. Probiotic organisms are generally beneficial components of microflora and confer normal health status. Usually, probiotics should be provided from the outside in the diet for maintaining proper health status. Probiotics can also have a significant impact on cancer management. While the results toward cancer management with probiotics are promising, careful risk assessment of probiotics use in cancer patients, who are usually immunocompromised due to radical therapy, comes as a great demand. This article provides an overview of the current research status of probiotics use in cancer patients and discusses the role of probiotics in cancer management. Drug Dev Res • • : • • – • • , 2013.
    Drug Development Research 09/2013; 74(6). DOI:10.1002/ddr.21087 · 0.73 Impact Factor
  • Source
    • "Collectively, there are over 800 species and 7000 strains that form over 100-trillion super colonies, which are influenced by several factors including diet, environment, stress, and disease (Burk et al., 2003; Vipperla and O'Keefe, 2012). Intestinal microbial composition has become an emerging factor in CRC susceptibility, since these organisms impact multiple physiological functions that are related to cancer progression, cell proliferation, differentiation, metabolism of essential nutrients, and stimulation of intestinal immunity; similarly, probiotics have been shown to prevent carcinogenesis through a variety of mechanisms (Zhu et al., 2011; Kumar et al., 2013). The fields of nutrition, microbiology , and genomics are converging rapidly, providing insight into the molecular mechanisms involved in the chemopreventive efficacy of probiotics; further fostering the development of inexpensive preventive therapies for CRC. "
    [Show abstract] [Hide abstract]
    ABSTRACT: One in four deaths in the United States is cancer-related, and colorectal cancer (CRC) is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; approximately 20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological, and behavioral processes that could influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.
    Frontiers in Oncology 05/2013; 3:119. DOI:10.3389/fonc.2013.00119
Show more