Hypoxia is considered as one of the most crucial elements of tumor microenvironment. The
hypoxia inducible
transcription factors (HIF-1/2) are used by the
cancer cells to adapt hypoxic microenvironment through regulating the expression of various target genes, including metabolic
enzymes.
Dimethyloxalylglycine (DMOG), a hypoxic mimetic used for HIF stabilisation in cell and animal models, also demonstrates multiple metabolic effects. In past, it was shown that in
cancer cells, DMOG treatment alters mitochondrial
ATP production, glycolysis, respiration etc. However, a global landscape of metabolic level alteration in
cancer cells during DMOG treatment is still not established. In the current work, the metabolic landscape of
cancer cells during DMOG treatment is explored by using untargeted metabolomics approach. Results showed that DMOG treatment primarily alters the one
carbon and lipid metabolism. The levels of one-
carbon metabolism related metabolites like
serine,
ornithine, and homomethionine levels significantly altered during DMOG treatment. Further, DMOG treatment reduces the global fatty acyls like
palmitic acids,
stearic acids, and
arachidonic acid levels in
cancer cell lines. Additionally, we found an alteration in glycolytic metabolites known to be regulated by
hypoxia in
cancer cell lines. Collectively, the results provided novel insights into the metabolic impact of DMOG on
cancer cells and showed that the use of DMOG to induce
hypoxia yields similar metabolic features relative to physiological
hypoxia.