Overview Of Metabolic Pathways Research Articles

Improving Natural Resistance to Cancer: An Overview of Metabolic Pathways in Cancer Cells Integrated with Regional Cancer Incidence Statistics

Context: Cellular metabolism is a set of controlled biochemical reactions known as metabolic pathways that occur in living organisms in order to sustain life. Cells may use different metabolic pathways and alter metabolism to use more effective processes for survival depending on cellular conditions. Alterations in metabolic pathways can lead to the transformation of normal cells into cancerous cells, leading to cancer initiation and development. Objectives: Proper cellular conditions in terms of pH and the availability of essential nutrients and oxygen are important for the healthy functioning of aerobically respiring human cells. If cells are exposed to stressors such as carcinogens that can induce mutations in the genes involved in metabolic pathways, anaerobic metabolism may be used by cells, turning them into cancerous cells. Cellular conditions that maintain aerobic cellular respiration and mitigate the effects of cellular stressors can improve cells’ resistance to neoplastic transformation. Methods: This paper explores the key metabolic pathways used by cancer cells as a function of their environmental conditions based on the Warburg effect. In addition, some analyses and studies were conducted on global and regional cancer incidence rates, taking into account changes in lifestyle and dietary patterns. Results and Conclusions: Natural resistance to cancer may be improved when cells grow in healthy conditions at molecular levels, requiring a balanced alkalizing diet and healthy lifestyle, as well as reduced exposure to environmental carcinogens, which are key control factors. In particular, effective nutritional interventions can help normal cells resist metabolic changes underlying cancer development.

Abstract 2505: High-resolution MRS characterization of malignant ascites in two models of ovarian cancer

Abstract Build-up of malignant ascites occurs in more than one third of ovarian cancer patients and significantly contributes to poor quality of life and mortality. Advances in understanding malignant ascites formation and finding new therapeutic options are urgently needed. High-resolution 1H MRS has been described as extremely useful in detecting endogenous metabolites to diagnose cancer, by providing a detailed overview of metabolic pathways in a single measurement. In the present study, we are using two ovarian cancer cell lines, the murine ID8-VEGF-Defb29 cell line and the human OVCAR3 cell line. Implanted orthotopically, these two ovarian cancer models are characterized by different profile of ascites formation. The mouse cell line ID8-VEGF-Defb29 induces large volumes of ascites, often more than 10 mL, while the human OVCAR3 cell line induces ascites less frequently and at smaller volumes, usually less than 0.2 mL. We applied high-resolution 1H MRS to compare the metabolic composition of both ascitic fluids. To better understand the differences observed, we characterized the metabolism of these ovarian cancer cells in culture by analyzing cell lysates and conditioned culture media with 1H MRS to advance our understanding of cancer cell metabolic reprogramming in malignant ascites formation and the role of the tumor microenvironment in ascites formation and composition. The two tumor models used in this study induced different ascitic profiles. While OVCAR3 tumor bearing mice developed small viscous volume of ascites, ID8-VEGF-Defb29 induced higher volumes. ID8-VEGF-Defb29 ascitic fluids were characterized by higher levels of glutamine, glucose, poly-unsaturated fatty acids and pyruvate compared to the OVCAR3 fluids, while all the other metabolites, including glutamate, lactate, myo-inositol, choline and acetate, were lower. To determine if the differences observed in the ascitic fluids were only due to a different metabolism of the cancer cells, we investigated their metabolism in vitro. We analyzed the metabolites present in the conditioned cell culture media, and in the cells, and observed differences in OVCAR3 and ID8-VEGF-Defb29 cells metabolism in vitro, without replicating the differences observed in vitro. A Venn diagram of the different metabolites present in the cells, media and ascites showed differences in the metabolites present in those 3 compartments, and highlighted the ones in common. Beta-hydroxybutyrate, lipids, maleic and citrate were found in both ascites, and not in the cells or media. Ascites MRS derived biomarkers could help in ovarian cancer diagnosis, and enhance our understanding of the biochemical and metabolic changes associated with ovarian cancer, and with ascites formation. Supported by Tina’s Wish Foundation, NIH P50CA013175 and P30CA06973. Citation Format: Santosh Bharti, Flonne Wildes, Chien-Fu Hung, TC Wu, Zaver Bhujwalla, Marie-France Penet. High-resolution MRS characterization of malignant ascites in two models of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2505. doi:10.1158/1538-7445.AM2017-2505

Nitrogen catabolite repression in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae the expression of all known nitrogen catabolite pathways are regulated by four regulators known as Gln3, Gat1, Dal80, and Deh1. This is known as nitrogen catabolite repression (NCR). They bind to motifs in the promoter region to the consensus sequence 5'GATAA 3'. Gln3 and Gat1 act positively on gene expression whereas Dal80 and Deh1 act negatively. Expression of nitrogen catabolite pathway genes known to be regulated by these four regulators are glutamine, glutamate, proline, urea, arginine. GABA, and allantonie. In addition, the expression of the genes encoding the general amino acid permease and the ammonium permease are also regulated by these four regulatory proteins. Another group of genes whose expression is also regulated by Gln3, Gat1, Dal80, and Deh1 are some proteases, CPS1, PRB1, LAP1, and PEP4, responsible for the degradation of proteins into amino acids thereby providing a nitrogen source to the cell. In this review, all known promoter sequences related to expression of nitrogen catabolite pathways are discussed as well as other regulatory proteins. Overview of metabolic pathways and promotors are presented.