Title: Exploring & exploiting the homeostasis network orchestration & biomarkers in human health: Disease prevention

Abstract

Background: The implications of disease in human are mostly addressed from the progression stage. For instance, Colorectal cancer is mostly diagnosed at age 50 years and above for non-hereditary colorectal cancer. Insufficient attention has been focused on understanding the early progression of diseases, particularly colorectal cancer, prior to the age in which most diagnosis occurs. Homeostasis biomarkers have not been given enough attention. Importantly, one of the key elements in homeostasis, glutathione, and its associated operating genes, have not been well elucidated in disease initiation, promotion, and progression. Additionally, the interplay theglutathione pathway has with other physiological functions and how they orchestrate in homeostasis is yet to be fully elucidated. Methods: Targeted quantitative analysis was performed on 41 samples of colon cancer and normal cell lines using capillary electrophoresis mass spectrometry (CE-TOFMS and CE-QqQMS) in the cation and anion analysis modes for analysing cationic and anionic metabolites, respectively. A total of 116 metabolites (54 and 62 metabolites in the cation and anion mode, respectively) involved in glycolysis, pentose phosphate pathway, tricarboxylic acid (TCA) cycle, urea cycle, and polyamine, creatine, purine,glutathione, nicotinamide, choline, and amino acid metabolisms were annotated based on the HMT metabolite database. Results: In both colon cancer cell lines, HCT-116 and HT-29, there were treatment effects from the addition of fiber and bile acids. Bile acid-A alone appeared to increase oxidative stress, osmotic stress, drive ATP demand and increase NAD+/NADH ratio – consistent with a tumor promoter role. Bile acid-B alone decreased levels of oxidative and osmotic stress and energy demand. Bile acid-B magnified decrease levels of oxidative and osmotic stress and energy demand when Bile acid-A and/or Fiber was added. The effects were similar between HCT-116 and HT-29, but not duplicative, as these are two different cancer cell lines. Conclusion: HCT-116 and HT-29 are colon cancer cell lines that exhibit proliferation in culture. Metabolomic profiling exhibits osmotic, energy and oxidative stress in these cell lines compared to normal colon cells. With different combinations of bile acids and fibres, it has been demonstrated that cellular stress in the colon cancer cells can be reduced to more normal levels.