Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

The circadian system temporally regulates physiology to maintain homeostasis. Co-opting and disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth and progression. Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumors respond to immune-based cancer therapeutics. While immuno-oncology has heralded a paradigm shift in cancer therapeutics, greater accuracy is needed to increase our capability of predicting who will respond favorably to, or who is likely to experience the troubling adverse effects of, immunotherapy. Insights into circadian signals may further refine our understanding of biological determinants of response and help answer the fundamental question of whether certain perturbations in circadian signals interfere with the activity of immune checkpoint inhibitors. Here we review the body of literature highlighting circadian disruption as a cancer promoter and synthesize the burgeoning evidence suggesting circadian signals play a role in how tumors respond to immune-based anti-cancer therapeutics. The goal is to develop a framework to advance our understanding of the relationships between circadian markers, cancer biology, and immunotherapeutics. Bolstered by this new understanding, these relationships may then be pursued in future clinical studies to improve our ability to predict which patients will respond favorably to, and avoid the adverse effects of, traditional and immune-based cancer therapeutics.

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Background: Bile acids have been implicated in oxidative damage via stimulation of reactive species including superoxide and nitric oxide. Superoxide and nitric oxide production are associated with inflammation. NF-κB up- regulation provides a critical link between inflammation and cancer. It has also been shown that there is a possible correlation between total activity of nitric oxide synthase and p53 mutation frequency in lung adenocarcinoma. Inulin is an oligosaccharide, classified as a prebiotic, and shown to improve gut health when used in combination with probiotics. However, there is paucity of data on how prebiotics alone affect gut health and by which mechanism of action. Objectives: To evaluate the potential of inulin in reduction of reactive species and its mechanism of inhibiting cancer cells. Methods: HCT116 adenocarcinoma cells were treated with inulin at different concentrations and stopped at various time ranges (30 minutes - 24 hours). Modified Greiss reagent was used in the study of reactive nitrogen species (RNS). Nitro blue tetrazolium (NBT) assay (Modified), was used in the investigation of superoxide production (SOP) in HCT116 in the presence of deoxycholic acids (DC); a secondary bile acids. Inulin (5%-40%) significantly inhibited DC (100μM-500 μM), generated RNS in HCT 116 cell lines (p<0.05; n = 6). The impact of inulin on RNS was observed to be dose and time-dependent. DC 100μM-300μM was observed to stimulate SOP in HCT116 (p<0.05; n = 3). Inulin (30%) was observed to inhibit SOP in HCT116 (P<0.05). The impact of inulin on RS was not enhanced in the presence of probiotics. Probiotic (Bifidobacterium longum) inhibited nitric oxide production (p<0.05; n = 3).The proliferation (Cyquant assay) of HCT116 was observed to be significantly influenced in the presence of DC; proliferation is inversely proportional to the concentration of DC; 100μM (p<0.05; n = 3) Proliferation of HCT 116 is enhanced in the presence of low concentration of DC <150 μM, while cell death and morphological change into mesenchymal cells is enhanced with >DC150μM. 30% Inulin enhanced cell death of morphologically changed cells in the presence of DC >150μM, with complete cell death occurring at DC300μM.Inulin inhibits proliferation of HCT 116 cancer cells. Inulin inhibits nitric oxide induced by DC p<0.05(n = 3) in normal human HK (keratinocytes) cells. Conclusions: Peroxynitrite is formed by nitric oxide and superoxide; and considered to be cytotoxic, causing DNA damage and leading to carcinogenesis via inactivation of tumour suppressor oncoprotein p53. Possible mechanism of action by which inulin could exert protective effect on colon cells could be via its antioxidant effect. Further work is underway investigating the effect of inulin and bile-acid on NF-κB, p53 and apoptosis in adenocarcinoma and normal dermal HK epithelial cells. Citation Format: Bene Akromaa Ekine-Afolabi, Sandra Appiah, Azra Pachenari, Lucy Ghali. Inulin inhibits free radical species in HCT 116 adenoma carcinoma and normal human HK (keratinocyte) cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-271. doi:10.1158/1538-7445.AM2015-LB-271

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