Heterogeneity in tumor cell energetic metabolome at different cell cycle phases of human colon cancer cell lines

Abstract

In this present study, the efficacy of metabolomics as a tool for tumor cell energetics for in vitro cell cultures was demonstrated with full competence for the first time by elucidating the anabolic and energy-yielding segments of glycolysis and glutaminolysis, which constitute a part of energy metabolism in tumor cells. By synchronizing colon cancer cells SW480 and SW620 in culture, the metabolome specific to cell cycle phases was analyzed using nuclear magnetic resonance spectroscopy. At the G 1 /S transition of the cell cycle (i.e. transition from cell growth to duplication of genetic material), the majority of the energy production was realized by glycolysis through a high channeling of glucose carbons towards lactate. During the late S phase, the majority of energy was produced by glutaminolysis through a high channeling of glutamine carbons towards lactate, while the glucose carbons were channeled towards bio-synthetic pathways. These results indicate that the metabolism of proliferating cells is heterogeneous throughout the cell cycle and can be better interpreted on the basis of different cell cycle phases. These findings could be exploited for the development of a tool for tumor diagnosis as well as for targeting tumors.

Biochemical fingerprint of colorectal cancer cell lines using label‐free live single‐cell Raman spectroscopy

“…Previous studies of xenographs of HT29, HCT116, and SW620 cells showed that the most common metabolites were amino acids and lactate, indicating that the 1,725 cm −1 peak associated with ν C=O and the 885 and 898 cm −1 peaks probably have a strong contribution from lactate. These peaks show the trend HCT116 > SW620 > HT29 > SW480 ≈ HL60, which also agrees with previous magnetic resonance spectroscopy results . This can be attributed to the Warburg effect, due to which highly proliferative cancerous cells have increased lactate contents; HCT116, SW620, and HT29 are known to have lower doubling times than SW480 and HL60 cells .…”

“…These peaks show the trend HCT116 > SW620 > HT29 > SW480 ≈ HL60, which also agrees with previous magnetic resonance spectroscopy results. [53,61] This can be attributed to the Warburg effect, due to which highly proliferative cancerous cells have increased lactate contents; HCT116, SW620, and HT29 are known to have lower doubling times than SW480 and HL60 cells. [51,[62][63][64] For the carcinoma cell lines, the lactate contribution appears to be correlated with the cancer stage.…”

“…Most of the peaks associated with saccharide contributions show higher contribution in the SW620 spectra. This could be explained by higher concentrations of glycolysis intermediates such as acetate or lactate [53] and an increased secretion of pericellular hyaluronan in SW620 compared with SW480 cells. [54] Peaks associated with phosphates also show a higher contribution for the SW620, which is in agreement with previous reports that showed an increase of the phosphorylated status of these cells.…”

Molecular histology analysis by matrix‐assisted laser desorption/ionization imaging mass spectrometry using gold nanoparticles as matrix

“…The region-specific characteristic ions could be attributed to the different metabolite profiles in the heterogeneous regions of the tumor resulting from different cellular activities and/or microenvironment. [22][23][24] The ion profiles of the different regions of the tumor tissue section are provided in Supplementary Fig. S5 (see Supporting Information).…”

Metabolic Profiling Comparison of Human Pancreatic Ductal Epithelial Cells and Three Pancreatic Cancer Cell Lines using NMR Based Metabonomics

“…Cancer cell lines are widely used to study potential therapeutic drugs, to identify proteins with altered expression levels, gene mutations, and inactivation or activation of metabolic pathways [ 12 – 14 ]. Several metabonomics studies have shown differences in metabolic profiles among different cancer cell lines [ 15 ] and the metabolic processes that occur during apoptosis and cell cycle phases [ 16 , 17 ]. In addition, monitoring metabolic profiles can also be useful to study the effect of various stimuli such as drug treatments [ 18 , 19 ].…”