High-Throughput Metabolomics for Identification of Metabolic Pathways and Deciphering the Effect Mechanism of Dioscin on Rectal Cancer From Cell Metabolic Profiles Coupled With Chemometrics Analysis

Abstract

High-throughput liquid chromatography-mass spectrometry (LC-MS)-based metabolomics can provide the holistic analysis of the low molecular weight endogenous metabolites in cells and reflect the changes of cellular regulation and metabolic pathways. Our study designed to reveal the potentially pharmacological effects of dioscin on SW480 rectal cancer cells using nontargeted metabolomics method to probe into small molecular metabolites and pathway changes. After the cell assay of proliferation, apoptosis, migration, and invasion, the dioscin-treated cell samples were prepared for nontargeted metabolomics analysis based on LC-MS tool to describe the metabolic profiles. Dioscin has prevented cell proliferation and accelerated cell apoptosis, and it also inhibited the SW480 rectal cancer cells' migration and invasion. A total of 22 metabolites were selected as promising biomarkers of pharmacological reaction of dioscin to rectal cancer, and eight highly correlated pathways including D-glutamine and D-glutamate metabolism, pyruvate metabolism, arachidonic acid metabolism, phenylalanine metabolism, tryptophan metabolism, glycolysis or gluconeogenesis, citrate cycle (TCA cycle), and butanoate metabolism were identified. It showed that strategies based on cell metabolomics are helpful tools to discover the small molecular metabolites to elucidate the action mechanism of drug.

Dioscin Alleviates Cardiac Dysfunction in Acute Myocardial Infarction via Rescuing Mitochondrial Malfunction

“…The in vivo reduction in the activities of Kreb's cycle in infarcted hearts may represent at an early maladaptive phase in the metabolic alterations after MI (24). It has been reported that highthroughput liquid chromatography-mass spectrometry (LC-MS)-based metabolomics demonstrate that dioscin could be associated with gluconeogenesis, Kreb's cycle, and butanoate metabolism (24). Consistently with the previous results, we further confirmed that dioscin is involved with Kreb's cycle.…”

“…The selective accumulation of the citric acid cycle intermediate succinate is a typical metabolic issue after infarction in a range of tissues, responsible for the accumulation of mitochondrial ROS production after reperfusion (23). The in vivo reduction in the activities of Kreb's cycle in infarcted hearts may represent at an early maladaptive phase in the metabolic alterations after MI (24). It has been reported that highthroughput liquid chromatography-mass spectrometry (LC-MS)-based metabolomics demonstrate that dioscin could be associated with gluconeogenesis, Kreb's cycle, and butanoate metabolism (24).…”

A host-specific diaminobutyrate aminotransferase contributes to symbiotic performance, homoserine metabolism, and competitiveness in the Rhizobium leguminosarum/Pisum sativum system

“…The pellets corresponding to around 10 7 cells were resuspended in 300 μL of cold methanol and disrupted with an ultrasonic probe (16 burst of 0.5 s per pulse at 80% intensity). After centrifugation at 15,000 × g , 15 min, 100 μL of the supernatant was transferred to a new tube and evaporated to dryness in a SpeedVac ( Wang et al, 2020 ). The metabolite extracts were re-suspended in 0.1 mol L −1 formic acid containing 0.2 mmol L −1 methionine sulfone (internal standard) by 1 min vortex mixing and then centrifuged (15,000 × g , 15 min).…”

Unravelling the Anticancer Mechanisms of Traditional Herbal Medicines with Metabolomics

“…involved in intermediary metabolism and whose levels are related to genetic expression (Figure 1). Metabolome reflects changes in enzyme activities, alteration in signalling pathways, catabolic and synthetic reactions [14].…”

“…involved in intermediary metabolism and whose levels are related to genetic expression (Figure 1). Metabolome reflects changes in enzyme activities, alteration in signalling pathways, catabolic and synthetic reactions [14]. The two main approaches in metabolomics are targeted (biased) and untargeted (unbiased) metabolite profiling.…”