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If BC is not diagnosed early, complications may lead to death. Thus, the pursuit of novel therapeutic avenues persists, notably focusing on epigenetic pathways such as histone deacetylases (HDACs). The compound N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), a derivative of valproic acid (VPA), has emerged as a promising candidate warranting pre-clinical investigation. HO-AAVPA is an HDAC inhibitor with antiproliferative effects on BC, but its molecular mechanism has yet to be deciphered. Furthermore, in the present study, we determined the metabolomic effects of HO-AAVPA and VPA on cells of luminal breast cancer (MCF-7) and triple-negative breast cancer (MDA-MB-231) subtypes. The LC-MS untargeted metabolomic study allowed for the simultaneous measurement of multiple metabolites and pathways, identifying that both compounds affect glycerophospholipid and sphingolipid metabolism in the MCF-7 and MDA-MB-231 cell lines, suggesting that other biological targets were different from HDACs. In addition, there are different dysregulate metabolites, possibly due to the physicochemical differences between HO-AAVPA and VPA.<\/jats:p>","DOI":"10.3390\/ijms241914543","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T03:53:00Z","timestamp":1695700380000},"page":"14543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Untargeted LC-MS\/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-834X","authenticated-orcid":false,"given":"Alan Rub\u00e9n","family":"Estrada-P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1930-5288","authenticated-orcid":false,"given":"Juan Benjam\u00edn","family":"Garc\u00eda-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-4281","authenticated-orcid":false,"given":"Humberto L.","family":"Mendoza-Figueroa","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0012-580X","authenticated-orcid":false,"given":"Martha Cecilia","family":"Rosales-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Fern\u00e1ndez-Pomares","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-5265","authenticated-orcid":false,"given":"Jos\u00e9","family":"Correa-Basurto","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.7150\/jca.18457","article-title":"Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping","volume":"8","author":"Dai","year":"2017","journal-title":"J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jama.2018.19323","article-title":"Breast Cancer Treatment","volume":"321","author":"Waks","year":"2019","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5420","DOI":"10.1038\/sj.onc.1210610","article-title":"Histone Deacetylases and Cancer","volume":"26","author":"Glozak","year":"2007","journal-title":"Oncogene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"371832","DOI":"10.1155\/2011\/371832","article-title":"Physical and Functional HAT\/HDAC Interplay Regulates Protein Acetylation Balance","volume":"2011","author":"Peserico","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Eckschlager, T., Plch, J., Stiborova, M., and Hrabeta, J. (2017). Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071414"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jprot.2016.10.003","article-title":"Lysine Acetylation and Cancer: A Proteomics Perspective","volume":"150","author":"Gil","year":"2017","journal-title":"J. Proteom."},{"key":"ref_9","first-page":"1677","article-title":"Histone Deacetylases 1, 6 and 8 Are Critical for Invasion in Breast Cancer","volume":"25","author":"Park","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1369\/0022155413506582","article-title":"Histone Deacetylases","volume":"62","author":"Parbin","year":"2013","journal-title":"J. Histochem. Cytochem."},{"key":"ref_11","first-page":"875824","article-title":"The Role of HDAC6 in Cancer","volume":"2011","author":"Sakamoto","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8797206","DOI":"10.1155\/2016\/8797206","article-title":"HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases","volume":"2016","author":"Hull","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biocel.2018.03.004","article-title":"HDAC Inhibitors as Epigenetic Regulators for Cancer Immunotherapy","volume":"98","author":"Conte","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.21873\/anticanres.11286","article-title":"Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer","volume":"37","author":"Damaskos","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI69738","article-title":"New and Emerging HDAC Inhibitors for Cancer Treatment","volume":"124","author":"West","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrd772","article-title":"Histone-Deacetylase Inhibitors: Novel Drugs for the Treatment of Cancer","volume":"1","author":"Johnstone","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Bishayee, A., and Pandey, A.K. (2018). Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy. Nutrients, 10.","DOI":"10.3390\/nu10060731"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"856985","DOI":"10.1155\/2011\/856985","article-title":"Manipulating Protein Acetylation in Breast Cancer: A Promising Approach in Combination with Hormonal Therapies?","volume":"2011","author":"Linares","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ddr.21268","article-title":"Impact of Histone Deacetylase Inhibitors on MicroRNA Expression and Cancer Therapy: A Review","volume":"76","author":"Ali","year":"2015","journal-title":"Drug Dev. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"a026831","DOI":"10.1101\/cshperspect.a026831","article-title":"HDACs and HDAC Inhibitors in Cancer Development and Therapy","volume":"6","author":"Li","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s10822-020-00304-2","article-title":"Exploring the Inhibitory Activity of Valproic Acid against the HDAC Family Using an MMGBSA Approach","volume":"34","author":"Bello","year":"2020","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12967-023-04015-8","article-title":"Valproic Acid Inhibits Cell Growth in Both MCF-7 and MDA-MB231 Cells by Triggering Different Responses in a Cell Type-Specific Manner","volume":"21","author":"Giordano","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s11033-021-06173-8","article-title":"Regulation of Valproic Acid Induced EMT by AKT\/GSK3\u03b2\/\u03b2-Catenin Signaling Pathway in Triple Negative Breast Cancer","volume":"48","author":"Ozman","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.canlet.2007.10.006","article-title":"Valproic Acid Is a Selective Antiproliferative Agent in Estrogen-Sensitive Breast Cancer Cells","volume":"259","author":"Fortunati","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.3892\/ijo.2015.3213","article-title":"Valproic acid inhibits proliferation of HER2-expressing breast cancer cells by inducing cell cycle arrest and apoptosis through Hsp70 acetylation","volume":"47","author":"Mawatari","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1210\/me.2008-0179","article-title":"Glucose Metabolism as a Target of Histone Deacetylase Inhibitors","volume":"23","author":"Wardell","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbrc.2018.11.103","article-title":"Valproic Acid Suppresses Warburg Effect and Tumor Progression in Neuroblastoma","volume":"508","author":"Fang","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"634874","DOI":"10.3389\/fmolb.2021.634874","article-title":"Butyrate Suppresses Glucose Metabolism of Colorectal Cancer Cells via GPR109a-AKT Signaling Pathway and Enhances Chemotherapy","volume":"8","author":"Geng","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chittur, S.V., Sangster-Guity, N., and McCormick, P.J. (2008). Histone Deacetylase Inhibitors: A New Mode for Inhibition of Cholesterol Metabolism. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-507"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11448","DOI":"10.1080\/07391102.2021.1955744","article-title":"Computational Study of DMPC Liposomes Loaded with the N-(2-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) and Determination of Its Antiproliferative Activity in Vitro in NIH-3T3 Cells","volume":"40","author":"Marcos","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.ijleo.2018.11.037","article-title":"Study of Nonlinear Properties of N-(2-Hydroxyphenyl)-2-Propylpentanamide in Polymeric Solution","volume":"180","year":"2019","journal-title":"Optik"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sixto-L\u00f3pez, Y., Rosales-Hern\u00e1ndez, M.C., de Oca, A.C.-M., Fragoso-Morales, L.G., Mendieta-Wejebe, J.E., Correa-Basurto, A.M., Abarca-Rojano, E., and Correa-Basurto, J. (2020). N-(2\u2032-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165873"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jpba.2018.09.010","article-title":"Pharmacokinetics and Tissue Distribution of N-(2-Hydroxyphenyl)-2-Propylpentanamide in Wistar Rats and Its Binding Properties to Human Serum Albumin","volume":"162","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/jphp.13270","article-title":"Exploring the Biotransformation of N-(2-hydroxyphenyl)-2-propylpentanamide (an Aryl Valproic Acid Derivative) by CYP2C11, Using in Silico Predictions and in Vitro Studies","volume":"72","author":"Bello","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"115033","DOI":"10.1016\/j.taap.2020.115033","article-title":"Anti-Epileptic Activity, Toxicity and Teratogenicity in CD1 Mice of a Novel Valproic Acid Arylamide Derivative, N-(2-Hydroxyphenyl)-2-Propylpentanamide","volume":"399","year":"2020","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"33368","DOI":"10.18632\/oncotarget.26077","article-title":"N-(2\u2032-Hydroxyphenyl)-2-propylpentanamide (OH-VPA), a histone deacetylase inhibitor, induces the release of nuclear HMGB1 and modifies ROS levels in HeLa cells","volume":"9","year":"2018","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1080\/14756366.2016.1210138","article-title":"N-(2-Hydroxyphenyl)-2-Propylpentanamide, a Valproic Acid Aryl Derivative Designed in Silico with Improved Anti-Proliferative Activity in HeLa, Rhabdomyosarcoma and Breast Cancer Cells","volume":"31","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Subramani, R., Poudel, S., Smith, K.D., Estrada, A., and Lakshmanaswamy, R. (2022). Metabolomics of Breast Cancer: A Review. Metabolites, 12.","DOI":"10.3390\/metabo12070643"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1586\/14789450.2013.840440","article-title":"Proteomics and Metabolomics in Cancer Drug Development","volume":"10","author":"Zolla","year":"2013","journal-title":"Expert Rev. Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/mas.20108","article-title":"Mass Spectrometry-based Metabolomics","volume":"26","author":"Dettmer","year":"2007","journal-title":"Mass Spectrom. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging Applications of Metabolomics in Drug Discovery and Precision Medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1007\/s13361-016-1469-y","article-title":"Untargeted Metabolomics Strategies\u2014Challenges and Emerging Directions","volume":"27","author":"Codreanu","year":"2016","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Estrada-P\u00e9rez, A.R., Rosales-Hern\u00e1ndez, M.C., Garc\u00eda-V\u00e1zquez, J.B., Bakalara, N., Fromager, B., and Correa-Basurto, J. (2022). Untargeted LC-MS\/MS Metabolomics Study on the MCF-7 Cell Line in the Presence of Valproic Acid. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052645"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1080\/00498254.2019.1618510","article-title":"Metabolomics Reveals the Effect of Valproic Acid on MCF-7 and MDA-MB-231 Cells","volume":"50","author":"Zhou","year":"2019","journal-title":"Xenobiotica"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1014798","DOI":"10.3389\/fcell.2022.1014798","article-title":"Metabolomic Profiling of Triple Negative Breast Cancer Cells Suggests That Valproic Acid Can Enhance the Anticancer Effect of Cisplatin","volume":"10","author":"Granit","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wawruszak, A., Luszczki, J.J., Grabarska, A., Gumbarewicz, E., Dmoszynska-Graniczka, M., Polberg, K., and Stepulak, A. (2015). Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines\u2014An Isobolographic Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143013"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hsu, K.-W., Huang, C.-Y., Tam, K.-W., Lin, C.-Y., Huang, L.-C., Lin, C.-L., Hsieh, W.-S., Chi, W.-M., Chang, Y.-J., and Wei, P.-L. (2018). The Application of Non-Invasive Apoptosis Detection Sensor (NIADS) on Histone Deacetylation Inhibitor (HDACi)-Induced Breast Cancer Cell Death. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020452"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cody, J.J., Markert, J.M., and Hurst, D.R. (2014). Histone Deacetylase Inhibitors Improve the Replication of Oncolytic Herpes Simplex Virus in Breast Cancer Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092919"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1093\/bioinformatics\/btq418","article-title":"MetPA: A Web-Based Metabolomics Tool for Pathway Analysis and Visualization","volume":"26","author":"Xia","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e532","DOI":"10.1038\/cddis.2013.60","article-title":"Targeting Cellular Metabolism to Improve Cancer Therapeutics","volume":"4","author":"Zhao","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40170-020-00237-2","article-title":"The Diversity and Breadth of Cancer Cell Fatty Acid Metabolism","volume":"9","author":"Nagarajan","year":"2021","journal-title":"Cancer Metab."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Schiliro, C., and Firestein, B.L. (2021). Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation. Cells, 10.","DOI":"10.3390\/cells10051056"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Burg, T., Rossaert, E., Moisse, M., Damme, P.V., and Bosch, L.V.D. (2021). Histone Deacetylase Inhibition Regulates Lipid Homeostasis in a Mouse Model of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011224"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of Fatty Acid Metabolism in Cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5393041","DOI":"10.1155\/2020\/5393041","article-title":"Resveratrol Modifies Lipid Composition of Two Cancer Cell Lines","volume":"2020","author":"Gomes","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Urias, B.S., Pavan, A.R., Albuquerque, G.R., Prokopczyk, I.M., Alves, T.M.F., de Melo, T.R.F., Sartori, G.R., da Silva, J.H.M., Chin, C.M., and Santos, J.L.D. (2022). Optimization of Resveratrol Used as a Scaffold to Design Histone Deacetylase (HDAC-1 and HDAC-2) Inhibitors. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101260"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Venturelli, S., Berger, A., B\u00f6cker, A., Busch, C., Weiland, T., Noor, S., Leischner, C., Schleicher, S., Mayer, M., and Weiss, T.S. (2013). Resveratrol as a Pan-HDAC Inhibitor Alters the Acetylation Status of Jistone Proteins in Human-Derived Hepatoblastoma Cells. PLoS ONE, 8.","DOI":"10.1371\/annotation\/5b9a8614-1009-40ca-b90b-db817fe445c9"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3389\/fphar.2019.00819","article-title":"Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity","volume":"10","author":"Xu","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_59","first-page":"163","article-title":"Valproate Uncompetitively Inhibits Arachidonic Acid Acylation by Rat Acyl-CoA Synthetase 4: Relevance to Valproate\u2019s Efficacy against Bipolar Disorder","volume":"1811","author":"Shimshoni","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Borin, T.F., Angara, K., Rashid, M.H., Achyut, B.R., and Arbab, A.S. (2017). Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122661"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1038\/s41467-018-07232-8","article-title":"Pan-Cancer Analysis of Transcriptional Metabolic Dysregulation Using the Cancer Genome Atlas","volume":"9","author":"Rosario","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.aca.2018.03.019","article-title":"Comparison of Modified Matyash Method to Conventional Solvent Systems for Polar Metabolite and Lipid Extractions","volume":"1037","author":"Sostare","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5279","DOI":"10.1007\/s00216-013-6927-9","article-title":"Optimization of Harvesting, Extraction, and Analytical Protocols for UPLC-ESI-MS-Based Metabolomic Analysis of Adherent Mammalian Cancer Cells","volume":"405","author":"Bi","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jpba.2017.07.044","article-title":"Quality Assurance Procedures for Mass Spectrometry Untargeted Metabolomics. a Review","volume":"147","author":"Dudzik","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"126","DOI":"10.4172\/jpb.1000360","article-title":"Liquid Chromatography-Mass Spectrometry Metabolic and Lipidomic Sample Preparation Workflow for Suspension-Cultured Mammalian Cells Using Jurkat T Lymphocyte Cells","volume":"8","author":"Ulmer","year":"2015","journal-title":"J. Proteom. Bioinform."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Walker, J.M. (1996). The Protein Protocols Handbook, Humana Press Inc.","DOI":"10.1007\/978-1-60327-259-9"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1645\/20-65","article-title":"Proteomic Analysis of Taenia Solium Cyst Fluid by Shotgun LC-MS\/MS","volume":"107","author":"Cui","year":"2021","journal-title":"J. Parasitol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"117327","DOI":"10.1016\/j.envpol.2021.117327","article-title":"Integrated Non-Targeted Lipidomics and Metabolomics Analyses for Fluctuations of Neonicotinoids Imidacloprid and Acetamiprid on Neuro-2a Cells","volume":"284","author":"Wang","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11306-018-1367-3","article-title":"Guidelines and Considerations for the Use of System Suitability and Quality Control Samples in Mass Spectrometry Assays Applied in Untargeted Clinical Metabolomic Studies","volume":"14","author":"Broadhurst","year":"2018","journal-title":"Metabolomics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.4155\/bio.12.204","article-title":"The Importance of Experimental Design and QC Samples in Large-Scale and MS-Driven Untargeted Metabolomic Studies of Humans","volume":"4","author":"Dunn","year":"2012","journal-title":"Bioanalysis"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Estrada-P\u00e9rez, A.R., Bakalara, N., Garc\u00eda-V\u00e1zquez, J.B., Rosales-Hern\u00e1ndez, M.C., Fern\u00e1ndez-Pomares, C., and Correa-Basurto, J. (2022). LC\u2013MS Based Lipidomics Depict Phosphatidylethanolamine as Biomarkers of TNBC MDA-MB-231 over NTNBC MCF-7 Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012074"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The Human Metabolome Database for 2022","volume":"50","author":"Wishart","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"W251","DOI":"10.1093\/nar\/gkv380","article-title":"MetaboAnalyst 3.0\u2014Making Metabolomics More Meaningful","volume":"43","author":"Xia","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41596-022-00710-w","article-title":"Using MetaboAnalyst 5.0 for LC\u2013HRMS Spectra Processing, Multi-Omics Integration and Covariate Adjustment of Global Metabolomics Data","volume":"17","author":"Pang","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1002\/cpbi.86","article-title":"Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis","volume":"68","author":"Chong","year":"2019","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nprot.2011.319","article-title":"Web-Based Inference of Biological Patterns, Functions and Pathways from Metabolomic Data Using MetaboAnalyst","volume":"6","author":"Xia","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"gkab382","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the Gap between Raw Spectra and Functional Insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:58:15Z","timestamp":1760129895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":77,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914543"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914543","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,26]]}}}