title: Enantioselective Effects of Metalaxyl Enantiomers on Breast Cancer Cells Metabolic Profiling Using HPLC-QTOF-Based Metabolomics.
abstract: In this study, an integrative high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF) based metabolomics approach was performed to evaluate the enantioselective metabolic perturbations in MCF-7 cells after treatment withR-metalaxyl andS-metalaxyl, respectively. Untargeted metabolomics profile, multivariate pattern recognition, metabolites identification, and pathway analysis were determined after metalaxyl enantiomer exposure. Principal component analysis (PCA) and partitial least-squares discriminant analysis (PLS-DA) directly reflected the enantioselective metabolic perturbations induced by metalaxyl enantiomers. On the basis of multivariate statistical results, a total of 49 metabolites including carbohydrates, amino acids, nucleotides, fatty acids, organic acids, phospholipids, indoles, derivatives, etc. were found to be the most significantly changed metabolites and metabolic fluctuations caused by the same concentration ofR-metalaxyl andS-metalaxyl were enantioselective. Pathway analysis indicated thatR-metalaxyl andS-metalaxyl mainly affected the 7 and 10 pathways in MCF-7 cells, respectively, implying the perturbed pathways induced by metalaxyl enantiomers were also enantioselective. Furthermore, the significantly perturbed metabolic pathways were highly related to energy metabolism, amino acid metabolism, lipid metabolism, and antioxidant defense. Such results provide more specific insights into the enantioselective metabolic effects of chiral pesticides in breast cancer progression, reveal the underlying mechanisms, and provide available data for the health risk assessments of chiral environmental pollutants at the molecular level.
authors.affiliation: College of Plant Protection, Southwest University, Chongqing 400715, China. pingz@swu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. wentaozhu@cau.edu.cn.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. wangdezhen@cau.edu.cn.
authors.forename: Dezhen
authors.initials: D
authors.lastname: Wang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. ping17028@gmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. yaow@cau.edu.cn.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Plant Protection, Southwest University, Chongqing 400715, China. helinok@vip.tom.com.
authors.forename: Lin
authors.initials: L
authors.lastname: He
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016002:Discriminant Analysis; D004734:Energy Metabolism / Q000187:drug effects; D005659:Fungicides, Industrial / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016018:Least-Squares Analysis; D061986:MCF-7 Cells; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D015394:Molecular Structure; D025341:Principal Component Analysis; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005659:Fungicides, Industrial; C028175:metalaxyl; D000409:Alanine
keywords: HPLC-QTOF; enantiomers; metabolic perturbations; metabolomics; metalaxyl