A biochemical comparison of the lung, colonic, brain, renal, and ovarian cancer cell lines using 1H-NMR spectroscopy

Abstract

Cancer cell lines are often used for cancer research. However, continuous genetic instability-induced heterogeneity of cell lines can hinder the reproducibility of cancer research. Molecular profiling approaches including transcriptomics, chromatin modification profiling, and proteomics are used to evaluate the phenotypic characteristics of cell lines. However, these do not reflect the metabolic function at the molecular level. Metabolic phenotyping is a powerful tool to profile the biochemical composition of cell lines. In the present study, 1H-NMR spectroscopy-based metabolic phenotyping was used to detect metabolic differences among five cancer cell lines, namely, lung (A549), colonic (Caco2), brain (H4), renal (RCC), and ovarian (SKOV3) cancer cells. The concentrations of choline, creatine, lactate, alanine, fumarate and succinate varied remarkably among different cell types. The significantly higher intracellular concentrations of glutathione, myo-inositol, and phosphocholine were found in the SKOV3 cell line relative to other cell lines. The concentration of glutamate was higher in both SKOV3 and RCC cells compared with other cell lines. For cell culture media analysis, isopropanol was found to be the highest in RCC media, followed by A549 and SKOV3 media, while acetone was the highest in A549, followed by RCC and SKOV3. These results demonstrated that 1H-NMR-based metabolic phenotyping approach allows us to characterize specific metabolic signatures of cancer cell lines and provides phenotypical information of cellular metabolism.

BCKDK alters the metabolism of non-small cell lung cancer

“…The alteration of tumor metabolism is closely related to the occurrence and progression of tumors (3). Tumor metabolism is generally characterized by increased lactic acid levels and decreased glutamine levels in blood circulation, and key enzymes in the metabolism of these substances have emerged as potential therapeutic targets (4). The advancement of metabolomics technology has led to the discovery of new and valuable differentially abundant metabolite (5)(6)(7)(8)(9), such as branched-chain amino acids (BCAAs).…”

Longitudinal MR spectroscopy to detect progression in patients with lower-grade glioma in the surveillance phase

“…Research connecting metabolic findings to the cellular and molecular underpinnings of higher-grade glioma biology has previously been done with glioblastoma cells lines, which showed high variability in metabolites as measured by MRSI and cell culture metabolites. 38 A similar study has not been done for LrGGs. Several studies have shown considerable upregulation of genomic and transcriptomic components of gliomas pertaining to metabolic pathway enzymes such as lactate dehydrogenase and creatine kinase with levels increasing with glioma grade.…”

Metabolomics in cancer and cancer-associated inflammatory cells

“…On the other hand, colon cancer cell lines showed increased levels of lactate, isovalerylcarnitine, and isobutiyrilcarnitine (degradation products of isoleucine and valine, respectively) [7] . Hu et al [51] compared the metabolic profiles of different tumor cell lines using MS. The distinct metabolic profile of each cell line was characterized by a unique phenotype.…”

“…However, intracellular analysis showed high glutamate concentrations in both RCC and SKOV3 cells, compared with those in other cells. Furthermore, lung cancer cells (A549) released higher concentrations of lactate but lower alanine levels, whereas brain tumor cells (H4) released high levels of serine, methionine, threonine, valine, glycine, and acetate [51] .…”