Metabolomic Signatures in Doxorubicin-Induced Metabolites Characterization, Metabolic Inhibition, and Signaling Pathway Mechanisms in Colon Cancer HCT116 Cells

Abstract

Doxorubicin (DOX) is a chemotherapeutic agent is used for various cancer cells. To characterize the chemical structural components and metabolic inhibition, we applied a DOX to HCT116 colon cancer cells using an independent metabolites profiling approach. Chemical metabolomics has been involved in the new drug delivery systems. Metabolomics profiling of DOX-applied HCT116 colon cancer cellular metabolisms is rare. We used 1H nuclear magnetic resonance (NMR) spectroscopy in this study to clarify how DOX exposure affected HCT116 colon cancer cells. Metabolomics profiling in HCT116 cells detects 50 metabolites. Tracking metabolites can reveal pathway activities. HCT116 colon cancer cells were evenly treated with different concentrations of DOX for 24 h. The endogenous metabolites were identified by comparison with healthy cells. We found that acetate, glucose, glutamate, glutamine, sn-glycero-3-phosphocholine, valine, methionine, and isoleucine were increased. Metabolic expression of alanine, choline, fumarate, taurine, o-phosphocholine, inosine, lysine, and phenylalanine was decreased in HCT116 cancer cells. The metabolic phenotypic expression is markedly altered during a high dose of DOX. It is the first time that there is a metabolite pool and phenotypic expression in colon cancer cells. Targeting the DOX-metabolite axis may be a novel strategy for improving the curative effect of DOX-based therapy for colon cancer cells. These methods facilitate the routine metabolomic analysis of cancer cells.

uL3 Regulates Redox Metabolism and Ferroptosis Sensitivity of p53-Deleted Colorectal Cancer Cells

“…Metabolite assignment was carried out through a multifaceted approach, which involved (i) scrutinizing existing literature data [23][24][25]; (ii) cross-referencing with the chemical shifts of metabolites cataloged in the Human Metabolome Database (HMDB), and (iii) employing the peak fitting algorithm integrated within the evaluation edition of Chenomx NMR Suite 8.4 software (Chenomx, AB, Canada).…”