Metabolomics is a branch of ‘omics’ sciences that utilises a couple of analytical tools for the identification of small molecules (metabolites) in a given sample. The overarching goal of metabolomics is to assess these metabolites quantitatively and qualitatively for their diagnostic, therapeutic, and prognostic potentials. Its use in various aspects of life has been documented. We have also published, howbeit in animal models, a few papers where metabolomic approaches were used in the study of metabolic disorders, such as metabolic syndrome, diabetes, and obesity. As the goal of every research is to benefit humankind, the purpose of this review is to provide insights into the applicability of metabolomics in medicine vis-à-vis its role in biomarker discovery for disease diagnosis and management. Here, important biomarkers with proven diagnostic and therapeutic relevance in the management of disease conditions, such as Alzheimer’s disease, dementia, Parkinson’s disease, inborn errors of metabolism (IEM), diabetic retinopathy, and cardiovascular disease, are noted.
Herein, we determined effect of guggulsterone (GS), a farnesoid X receptor antagonist, on 14-3-3 zeta associated molecular pathways for abrogation of apoptosis in head and neck cancer cells. Head and neck cancer cells were treated with guggulsterone (GS). Effect of GS-treatment was evaluated using cell viability (MTT) assay and apoptosis was verified by annexin V, DNA fragmentation and M30 CytoDeath antibody assay. Mechanism of GS-induced apoptosis was determined by western blotting and co-IP assays using specific antibodies. Using in vitro models of head and neck cancer, we showed 14-3-3 zeta as a key player regulating apoptosis in GS treated SCC4 cells. Treatment with GS releases BAD from the inhibitory action of 14-3-3 zeta in proliferating HNSCC cells by activating protein phosphatase 2A (PP2A). These events initiate the intrinsic mitochondrial pathway of apoptosis, as revealed by increased levels of cytochrome c in cytoplasmic extracts of GS-treated SCC4 cells. In addition, GS treatment significantly reduced the expression of anti-apoptotic proteins, Bcl-2, xIAP, Mcl1, survivin, cyclin D1 and c-myc, thus committing cells to apoptosis. These events were followed by activation of caspase 9, caspase 8 and caspase 3 leading to cleavage of its downstream target, poly-ADP-ribose phosphate (PARP).