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      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

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          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.

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          Most cited references54

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          Primary prevention of colorectal cancer.

          Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence.
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            Metabolomics in diagnosis and biomarker discovery of colorectal cancer.

            Colorectal cancer (CRC), a major public health concern, is the second leading cause of cancer death in developed countries. There is a need for better preventive strategies to improve the patient outcome that is substantially influenced by cancer stage at the time of diagnosis. Patients with early stage colorectal have a significant higher 5-year survival rates compared to patients diagnosed at late stage. Although traditional colonoscopy remains the effective means to diagnose CRC, this approach generally suffers from poor patient compliance. Thus, it is important to develop more effective methods for early diagnosis of this disease process, also there is an urgent need for biomarkers to diagnose CRC, assess disease severity, and prognosticate course. Increasing availability of high-throughput methodologies open up new possibilities for screening new potential candidates for identifying biomarkers. Fortunately, metabolomics, the study of all metabolites produced in the body, considered most closely related to a patient's phenotype, can provide clinically useful biomarkers applied in CRC, and may now open new avenues for diagnostics. It has a largely untapped potential in the field of oncology, through the analysis of the cancer metabolome to identify marker metabolites defined here as surrogate indicators of physiological or pathophysiological states. In this review we take a closer look at the metabolomics used within the field of colorectal cancer. Further, we highlight the most interesting metabolomics publications and discuss these in detail; additional studies are mentioned as a reference for the interested reader.
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              Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research.

              Mass spectrometry-based metabolomics has become increasingly popular in molecular medicine. High-definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low-molecular-weight metabolites in bio-samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS-based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS-metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                28 February 2020
                2020
                : 11
                : 68
                Affiliations
                [1] 1Heilongjiang Province Land Reclamation Headquarters General Hospital, Heilongjiang Agriculture and Reclamation Bureau , Harbin, China
                [2] 2College of Traditional Chinese Medicine, Jilin Agricultural University , Changchun, China
                [3] 3Department of Orthopedics, The Affiliated First Hospital of Heilongjiang University of Chinese Medicine , Harbin, China
                Author notes

                Edited by: Lyndy Joy McGaw, University of Pretoria, South Africa

                Reviewed by: Jianping Chen, Shenzhen Traditional Chinese Medicine Hospital, China; Xijun Wang, Heilongjiang University of Chinese Medicine, China

                *Correspondence: Xin-Xin Wang, xinxinwang79@ 123456sina.cn

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work

                Article
                10.3389/fphar.2020.00068
                7059176
                32322201
                7245a080-94a2-48ec-8738-bf4e2a07dd68
                Copyright © 2020 Wang, Yu and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 July 2019
                : 24 January 2020
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 63, Pages: 11, Words: 4859
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                metabolomics,biomarker,natural product,metabolic pathways,mass spectrometry

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