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individual Ph.D. fellowship","award":["AAC 01\/SAICT\/2016"],"award-info":[{"award-number":["AAC 01\/SAICT\/2016"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["UIDB\/04612\/2020"],"award-info":[{"award-number":["UIDB\/04612\/2020"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["UIDP\/04612\/2020"],"award-info":[{"award-number":["UIDP\/04612\/2020"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["UI\/BD\/154203\/2022"],"award-info":[{"award-number":["UI\/BD\/154203\/2022"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["SFRH\/BPD\/111100\/2015"],"award-info":[{"award-number":["SFRH\/BPD\/111100\/2015"]}]},{"name":"CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT","award":["AAC 01\/SAICT\/2016"],"award-info":[{"award-number":["AAC 01\/SAICT\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: The cell-free DNA (cfDNA) is an extracellular fragmented DNA found in body fluids in physiological and pathophysiological contexts. In cancer, cfDNA has been pointed out as a marker for disease diagnosis, staging, and prognosis; however, little is known about its biological role. Methods: The role of cfDNA released by ES-2 ovarian cancer cells was investigated, along with the impact of glucose bioavailability and culture duration in the cfDNA-induced phenotype. The effect of cfDNA on ES-2 cell proliferation was evaluated by proliferation curves, and cell migration was assessed through wound healing. We explored the impact of different cfDNA variants on ES-2 cells\u2019 metabolic profile using nuclear magnetic resonance (NMR) spectroscopy and cisplatin resistance through flow cytometry. Moreover, we assessed the protein levels of DNA-sensitive Toll-like receptor 9 (TLR9) by immunofluorescence and its colocalization with lysosome-associated membrane protein 1 (LAMP1). Results: This study demonstrated that despite inducing similar effects, different variants of cfDNA promote different effects on cells derived from the ES-2 cell line. We observed instant reactions of adopting the metabolic profile that brings back the cell functioning of more favorable culture conditions supporting proliferation and resembling the cell of origin of the cfDNA variant, as observed in unselected ES-2 cells. However, as a long-term selective factor, certain cfDNA variants induced quiescence that favors the chemoresistance of a subset of cancer cells. Conclusions: Therefore, different tumoral microenvironments may generate cfDNA variants that will impact cancer cells differently, orchestrating the disease fate.<\/jats:p>","DOI":"10.3390\/metabo15040244","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T07:47:44Z","timestamp":1743580064000},"page":"244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling in the ES-2 Ovarian Carcinoma Cell Line, Influencing Cell Proliferation, Quiescence, and Chemoresistance in a Cell-of-Origin-Specific Manner"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-905X","authenticated-orcid":false,"given":"Isabel","family":"Lemos","sequence":"first","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7570-0066","authenticated-orcid":false,"given":"Catarina","family":"Freitas-Dias","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal"}]},{"given":"Ana","family":"Hip\u00f3lito","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1927-164X","authenticated-orcid":false,"given":"Jos\u00e9","family":"Ramalho","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-1132","authenticated-orcid":false,"given":"Fabrizio","family":"Carteni","sequence":"additional","affiliation":[{"name":"Lab Applied Ecology and System Dynamics, Dipartimento di Agraria, Universit\u00e0 di Napoli \u201cFederico II\u201d, Portici, 80055 Naples, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-3552","authenticated-orcid":false,"given":"Lu\u00eds G.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Avenida da Rep\u00fablica (EAN), 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-2625","authenticated-orcid":false,"given":"Stefano","family":"Mazzoleni","sequence":"additional","affiliation":[{"name":"Lab Applied Ecology and System Dynamics, Dipartimento di Agraria, Universit\u00e0 di Napoli \u201cFederico II\u201d, Portici, 80055 Naples, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1548-5907","authenticated-orcid":false,"given":"Jacinta","family":"Serpa","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103109","DOI":"10.1016\/j.critrevonc.2020.103109","article-title":"ctDNA as a cancer biomarker: A broad overview","volume":"155","author":"Pessoa","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Telekes, A., and Horv\u00e1th, A. (2022). The Role of Cell-Free DNA in Cancer Treatment Decision Making. Cancers, 14.","DOI":"10.3390\/cancers14246115"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.aca.2017.12.050","article-title":"Review: Microfluidics technologies for blood-based cancer liquid biopsies","volume":"1012","author":"Sun","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_4","first-page":"241","article-title":"Nuclear Acids In Human Blood Plasma","volume":"142","author":"Mandel","year":"1948","journal-title":"C R. Seances Soc. Biol. Fil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1749-6632.2000.tb06608.x","article-title":"The origin and mechanism of circulating DNA","volume":"906","author":"Stroun","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ivanov, M., Baranova, A., Butler, T., Spellman, P., and Mileyko, V. (2015). Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation. BMC Genom., 16.","DOI":"10.1186\/1471-2164-16-S13-S1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cell.2015.11.050","article-title":"Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-of-Origin","volume":"164","author":"Snyder","year":"2016","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1196\/annals.1448.002","article-title":"Overview of circulating nucleic acids in plasma\/serum","volume":"1137","author":"Butt","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1158\/1541-7786.MCR-16-0044","article-title":"Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped By Emerging Technologies","volume":"14","author":"Volik","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_10","first-page":"646","article-title":"Free DNA in the serum of cancer patients and the effect of therapy","volume":"37","author":"Leon","year":"1977","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yan, Y.Y., Guo, Q.R., Wang, F.H., Adhikari, R., Zhu, Z.Y., Zhang, H.Y., Zhou, W.M., Yu, H., Li, J.Q., and Zhang, J.Y. (2021). Cell-Free DNA: Hope and Potential Application in Cancer. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.639233"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.molmed.2020.01.012","article-title":"Cell-free DNA and apoptosis: How dead cells inform about the living","volume":"26","author":"Heitzer","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bronkhorst, A.J., Ungerer, V., and Holdenrieder, S. (2019). The emerging role of cell-free DNA as a molecular marker for cancer management. Biomol. Detect. Quantif., 17.","DOI":"10.1016\/j.bdq.2019.100087"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Muinelo-Romay, L., Casas-Arozamena, C., and Abal, M. (2018). Liquid Biopsy in Endometrial Cancer: New Opportunities for Personalized Oncology. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082311"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.critrevonc.2017.12.002","article-title":"Circulating tumour DNA, a promising biomarker for the management of colorectal cancer","volume":"122","author":"Khakoo","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cell.2018.11.046","article-title":"Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding","volume":"176","author":"Gkountela","year":"2019","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12943-019-0989-z","article-title":"The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis","volume":"18","author":"Zhang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.1002\/cam4.2560","article-title":"Ovarian cancer: Current status and strategies for improving therapeutic outcomes","volume":"8","author":"Chandra","year":"2019","journal-title":"Cancer Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/S0140-6736(13)62146-7","article-title":"Ovarian cancer","volume":"384","author":"Jayson","year":"2014","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nrc2946","article-title":"The genesis and evolution of high-grade serous ovarian cancer","volume":"10","author":"Bowtell","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrc2644","article-title":"The biology of ovarian cancer: New opportunities for translation","volume":"9","author":"Bast","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5528\/wjtm.v3.i1.1","article-title":"Epithelial ovarian cancer: An overview","volume":"3","author":"Desai","year":"2014","journal-title":"World J. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00428-012-1203-5","article-title":"Ovarian carcinomas: Five distinct diseases with different origins, genetic alterations, and clinicopathological features","volume":"460","author":"Prat","year":"2012","journal-title":"Virchows Arch."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Alatise, K.L., Gardner, S., and Alexander-Bryant, A. (2022). Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets. Cancers, 14.","DOI":"10.3390\/cancers14246246"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.ygyno.2021.06.033","article-title":"Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes","volume":"162","author":"Gadducci","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.ygyno.2012.04.021","article-title":"Clear cell carcinoma of the ovary: A review of the literature","volume":"126","author":"Birrer","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1007\/s13277-015-4290-5","article-title":"HNF1\u03b2 drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC)","volume":"37","author":"Nunes","year":"2016","journal-title":"Tumour. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.ygyno.2021.06.028","article-title":"Cell-free DNA is abundant in ascites and represents a liquid biopsy of ovarian cancer","volume":"162","author":"Werner","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1002\/1878-0261.13710","article-title":"Cell-free DNA from ascites identifies clinically relevant variants and tumour evolution in patients with advanced ovarian cancer","volume":"18","author":"Werner","year":"2024","journal-title":"Mol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"779","DOI":"10.4143\/crt.2019.700","article-title":"Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer","volume":"52","author":"Han","year":"2020","journal-title":"Cancer Res. Treat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13048-022-01068-z","article-title":"Can circulating cell free DNA be a promising marker in ovarian cancer?\u2014A genome-scale profiling study in a single institution","volume":"16","author":"Zhou","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nunes, S.C., Ramos, C., Lopes-Coelho, F., Sequeira, C.O., Silva, F., Gouveia-Fernandes, S., Rodrigues, A., Guimar\u00e3es, A., Silveira, M., and Abreu, S. (2018). Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27753-y"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nunes, S.C., Ramos, C., Santos, I., Mendes, C., Silva, F., Vicente, J.B., Pereira, S.A., F\u00e9lix, A., Gon\u00e7alves, L.G., and Serpa, J. (2021). Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.722412"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12943-022-01588-8","article-title":"Potential clinical utility of liquid biopsies in ovarian cancer","volume":"21","author":"Zhu","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"627","DOI":"10.37349\/etat.2024.00239","article-title":"Clinical relevance of circulating tumor DNA in ovarian cancer: Current issues and future opportunities","volume":"5","author":"Trevisi","year":"2024","journal-title":"Explor. Target. Antitumor. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1080\/15384101.2018.1442622","article-title":"Revisiting the Crabtree\/Warburg effect in a dynamic perspective: A fitness advantage against sugar-induced cell death","volume":"17","author":"Parascandola","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/ars.2011.4391","article-title":"The cystine\/glutamate antiporter system x(c)(-) in health and disease: From molecular mechanisms to novel therapeutic opportunities","volume":"18","author":"Lewerenz","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling","volume":"7","author":"Bowie","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbrc.2009.09.009","article-title":"Early growth response-1 is involved in foam cell formation and is upregulated by the TLR9\u2013MyD88\u2013ERK1\/2 pathway","volume":"390","author":"Kim","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-60761-411-1_4","article-title":"Identification of ROS using oxidized DCFDA and flow-cytometry","volume":"594","author":"Eruslanov","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41392-020-00216-5","article-title":"The interaction between ferroptosis and lipid metabolism in cancer","volume":"5","author":"Li","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0891-5849(02)00848-1","article-title":"C11-BODIPY581\/591, an oxidation-sensitive fluorescent lipid peroxidation probe:(micro) spectroscopic characterization and validation of methodology","volume":"33","author":"Drummen","year":"2002","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mitra, M., Ho, L.D., and Coller, H.A. (2018). An in vitro Model of Cellular Quiescence in Primary Human Dermal Fibroblasts, Springer.","DOI":"10.1007\/978-1-4939-7371-2_2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10555-022-10073-z","article-title":"Dormant cancer cells: Programmed quiescence, senescence, or both?","volume":"42","author":"Truskowski","year":"2023","journal-title":"Cancer Metastasis. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mungai, R.W., Hartman, R.J., Jolin, G.E., Piskorowski, K.W., and Billiar, K.L. (2024). Towards a more objective and high-throughput spheroid invasion assay quantification method. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-82191-3"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lindell, E., Zhong, L., and Zhang, X. (2023). Quiescent Cancer Cells\u2014A Potential Therapeutic Target to Overcome Tumor Resistance and Relapse. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043762"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cvetkovi\u0107, D., Goertzen, C.G.-F., and Bhattacharya, M. (2014). Quantification of breast cancer cell invasiveness using a three-dimensional (3D) model. J. Vis. Exp. JoVE, 51341.","DOI":"10.3791\/51341"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tevis, K.M., Colson, Y.L., and Grinstaff, M.W. (2017). Embedded spheroids as models of the cancer microenvironment. Adv. Biosyst., 1.","DOI":"10.1002\/adbi.201700083"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Nunes, S.C., Lopes-Coelho, F., Gouveia-Fernandes, S., Ramos, C., Pereira, S.A., and Serpa, J. (2018). Cysteine boosters the evolutionary adaptation to CoCl(2) mimicked hypoxia conditions, favouring carboplatin resistance in ovarian cancer. BMC Evol. Biol., 18.","DOI":"10.1186\/s12862-018-1214-1"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2147\/JEP.S267383","article-title":"Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin in Cancer Therapy","volume":"13","author":"Tchounwou","year":"2021","journal-title":"J. Exp. Pharmacol."},{"key":"ref_52","first-page":"209","article-title":"Free-radical mechanisms in tissue injury","volume":"222","author":"Slater","year":"1984","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0021-5198(19)43504-X","article-title":"Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues","volume":"43","author":"Sugihara","year":"1987","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.4049\/jimmunol.0900399","article-title":"Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes","volume":"183","author":"Yasuda","year":"2009","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/icb.2008.101","article-title":"TLR9 traffics through the Golgi complex to localize to endolysosomes and respond to CpG DNA","volume":"87","author":"Chockalingam","year":"2009","journal-title":"Immunol. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.shpsc.2017.04.001","article-title":"Cancer is a propagandist","volume":"63","author":"Fantuzzi","year":"2017","journal-title":"Stud. Hist. Philos. Biol. Biomed. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5832","DOI":"10.1158\/1078-0432.CCR-18-4049","article-title":"Analysis of Cell-Free DNA from 32,989 Advanced Cancers Reveals Novel Co-occurring Activating RET Alterations and Oncogenic Signaling Pathway Aberrations","volume":"25","author":"Rich","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_58","first-page":"9467029","article-title":"Oxidized Cell-Free DNA Is a Factor of Stress Signaling in Radiation-Induced Bystander Effects in Different Types of Human Cells","volume":"2019","author":"Konkova","year":"2019","journal-title":"Int. J. Genom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1093\/ije\/dyl185","article-title":"The population dynamics of cancer: A Darwinian perspective","volume":"35","author":"Vineis","year":"2006","journal-title":"Int. J. Epidemiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"109979","DOI":"10.1016\/j.isci.2024.109979","article-title":"Hallmarks of cancer resistance","volume":"27","author":"Tufail","year":"2024","journal-title":"iScience"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Dodes Traian, M.M., Cattoni, D.I., Levi, V., and Gonz\u00e1lez Flecha, F.L. (2012). A two-stage model for lipid modulation of the activity of integral membrane proteins. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039255"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1074\/jbc.M114.585828","article-title":"Modulation of plasma membrane Ca2+-ATPase by neutral phospholipids: Effect of the micelle-vesicle transition and the bilayer thickness","volume":"290","author":"Pignataro","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s10555-021-10007-1","article-title":"Extracellular citrate and metabolic adaptations of cancer cells","volume":"40","author":"Parkinson","year":"2021","journal-title":"Cancer Metastasis. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Drexler, K., Schmidt, K.M., Jordan, K., Federlin, M., Milenkovic, V.M., Liebisch, G., Artati, A., Schmidl, C., Madej, G., and Tokarz, J. (2021). Cancer-associated cells release citrate to support tumour metastatic progression. Life Sci. Alliance, 4.","DOI":"10.26508\/lsa.202000903"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.drudis.2016.12.003","article-title":"Targeting amino acid metabolism for cancer therapy","volume":"22","author":"Lukey","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.chembiol.2017.08.028","article-title":"Targeting metabolism for cancer therapy","volume":"24","author":"Luengo","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/PPO.0000000000000104","article-title":"Alternative fuels for cancer cells","volume":"21","author":"Keenan","year":"2015","journal-title":"Cancer J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nchembio.1961","article-title":"Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis","volume":"12","author":"Green","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Moffatt, B.A., and Ashihara, H. (2002). Purine and pyrimidine nucleotide synthesis and metabolism. Arab. Book\/Am. Soc. Plant Biol., 1.","DOI":"10.1199\/tab.0018"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6747","DOI":"10.1038\/s41388-020-01480-z","article-title":"Multifaceted role of branched-chain amino acid metabolism in cancer","volume":"39","author":"Peng","year":"2020","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41419-024-06435-w","article-title":"Amino acid metabolism in tumor biology and therapy","volume":"15","author":"Chen","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.canlet.2021.06.020","article-title":"Metabolism and function of polyamines in cancer progression","volume":"519","author":"Sari","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1006\/bbrc.1998.8258","article-title":"Structural specificity of polyamines and polyamine analogues in the protection of DNA from strand breaks induced by reactive oxygen species","volume":"244","author":"Ha","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"25218","DOI":"10.1074\/jbc.274.36.25218","article-title":"L-arginine binding to nitric-oxide synthase. The role of H-bonds to the nonreactive guanidinium nitrogens","volume":"274","author":"Babu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chen, L., Tang, Q., Zhang, K., Huang, Q., Ding, Y., Jin, B., Liu, S., Hwa, K., Chou, C.J., and Zhang, Y. (2023). Altered expression of the L-arginine\/nitric oxide pathway in ovarian cancer: Metabolic biomarkers and biological implications. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11192-8"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Daverio, Z., Balcerczyk, A., Rautureau, G.J.P., and Panthu, B. (2023). How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation. Cancers, 15.","DOI":"10.3390\/cancers15051417"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"101093","DOI":"10.1016\/j.molmet.2020.101093","article-title":"Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment","volume":"42","author":"Maeda","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"jcs260787","DOI":"10.1242\/jcs.260787","article-title":"The role of metabolism in cellular quiescence","volume":"136","author":"Du","year":"2023","journal-title":"J. Cell Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1042\/bj3120163","article-title":"A hierarchy of ATP-consuming processes in mammalian cells","volume":"312","author":"Buttgereit","year":"1995","journal-title":"Biochem. J."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chen, J.L.-Y., Merl, D., Peterson, C.W., Wu, J., Liu, P.Y., Yin, H., Muoio, D.M., Ayer, D.E., West, M., and Chi, J.-T. (2010). Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001093"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ccell.2019.12.011","article-title":"Emerging roles for branched-chain amino acid metabolism in cancer","volume":"37","author":"Sivanand","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_82","unstructured":"Dang, C., Gilewski, T.A., Surbone, A., and Norton, L. (2003). Growth curve analysis. Holland-Frei Cancer Medicine, BC Decker. [6th ed.]."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2174\/1574888X0902140121163539","article-title":"Comparison of the growth curves of cancer cells and cancer stem cells","volume":"9","author":"Toloudi","year":"2014","journal-title":"Curr. Stem. Cell Res. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s41580-019-0123-5","article-title":"Metabolic regulation of cell growth and proliferation","volume":"20","author":"Zhu","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/path.5395","article-title":"The stressful tumour environment drives plasticity of cell migration programmes, contributing to metastasis","volume":"250","author":"Nikolaou","year":"2020","journal-title":"J. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cmet.2018.11.018","article-title":"Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming","volume":"29","author":"Goding","year":"2019","journal-title":"Cell Metab."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Deng, S., Leong, H.C., Datta, A., Gopal, V., Kumar, A.P., and Yap, C.T. (2022). PI3K\/AKT signaling tips the balance of cytoskeletal forces for cancer progression. Cancers, 14.","DOI":"10.3390\/cancers14071652"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40591-015-0041-7","article-title":"Cross talk of the first-line defense TLRs with PI3K\/Akt pathway, in preconditioning therapeutic approach","volume":"3","author":"Pourrajab","year":"2015","journal-title":"Mol. Cell. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Lima, B.H.F., Marques, P.E., Gomides, L.F., Mattos, M.S., Kraemer, L., Queiroz-Junior, C.M., Lennon, M., Hirsch, E., Russo, R.C., and Menezes, G.B. (2019). Converging TLR9 and PI3Kgamma signaling induces sterile inflammation and organ damage. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55504-0"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Endo, H., Owada, S., Inagaki, Y., Shida, Y., and Tatemichi, M. (2018). Glucose starvation induces LKB1-AMPK-mediated MMP-9 expression in cancer cells. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28074-w"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vomund, S., Sch\u00e4fer, A., Parnham, M.J., Br\u00fcne, B., and Von Knethen, A. (2017). Nrf2, the master regulator of anti-oxidative responses. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122772"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1159\/000519784","article-title":"The pentose phosphate pathway in cancer: Regulation and therapeutic opportunities","volume":"66","author":"Ghanem","year":"2021","journal-title":"Chemotherapy"},{"key":"ref_93","first-page":"292","article-title":"Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation","volume":"10","author":"Incerti","year":"2023","journal-title":"Microb. Cell"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Palomba, E., Chiusano, M.L., Monticolo, F., Langella, M.C., Sanchez, M., Tirelli, V., de Alteriis, E., Iannaccone, M., Termolino, P., and Capparelli, R. (2024). Extracellular Self-DNA Effects on Yeast Cell Cycle and Transcriptome during Batch Growth. Biomolecules, 14.","DOI":"10.3390\/biom14060663"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41419-021-04116-6","article-title":"The metabolic flexibility of quiescent CSC: Implications for chemotherapy resistance","volume":"12","author":"Chen","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.semcancer.2019.09.007","article-title":"Cancer stem cells and their unique role in metastatic spread","volume":"60","author":"Steinbichler","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/s41467-024-46524-0","article-title":"Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory","volume":"15","author":"Michelatti","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_98","unstructured":"Martin, T.A., Ye, L., Sanders, A.J., Lane, J., and Jiang, W.G. (2013). Cancer invasion and metastasis: Molecular and cellular perspective. Madame Curie Bioscience Database, Landes Bioscience."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1101\/gad.277681.116","article-title":"Distinctive properties of metastasis-initiating cells","volume":"30","author":"Kang","year":"2016","journal-title":"Genes. Dev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.18632\/oncotarget.14021","article-title":"Chemoresistance and targeted therapies in ovarian and endometrial cancers","volume":"8","author":"Brasseur","year":"2017","journal-title":"Oncotarget"},{"key":"ref_101","first-page":"1440","article-title":"Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells","volume":"89","author":"Schnelldorfer","year":"2000","journal-title":"Cancer Interdiscip. Int. J. Am. Cancer Soc."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/cbf.1149","article-title":"The role of glutathione in cancer","volume":"22","author":"Balendiran","year":"2004","journal-title":"Cell Biochem. Funct."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1083\/jcb.201804161","article-title":"Glutathione metabolism in cancer progression and treatment resistance","volume":"217","author":"Bansal","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Kostyuk, S.V., Konkova, M.S., Ershova, E.S., Alekseeva, A.J., Smirnova, T.D., Stukalov, S.V., Kozhina, E.A., Shilova, N.V., Zolotukhina, T.V., and Markova, Z.G. (2013). An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077469"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1517\/14712598.2012.688948","article-title":"Extracellular DNA oxidation stimulates activation of NRF2 and reduces the production of ROS in human mesenchymal stem cells","volume":"12","author":"Loseva","year":"2012","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1245749","DOI":"10.1155\/2019\/1245749","article-title":"Oxidized Cell-Free DNA Role in the Antioxidant Defense Mechanisms under Stress","volume":"2019","author":"Filev","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Combs, J.A., and DeNicola, G.M. (2019). The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival. Cancers, 11.","DOI":"10.3390\/cancers11050678"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/sj.bjc.6600786","article-title":"Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines","volume":"88","author":"Okuno","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/s41467-017-00695-1","article-title":"BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells","volume":"8","author":"Combes","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/ni.1669","article-title":"Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9","volume":"9","author":"Park","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.4049\/jimmunol.1502357","article-title":"Complex negative regulation of TLR9 by multiple proteolytic cleavage events","volume":"197","author":"Sinha","year":"2016","journal-title":"J. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4049\/jimmunol.174.1.456","article-title":"In vivo ethanol exposure down-regulates TLR2-, TLR4-, and TLR9-mediated macrophage inflammatory response by limiting p38 and ERK1\/2 activation","volume":"174","author":"Goral","year":"2005","journal-title":"J. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/emm.2007.27","article-title":"Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression","volume":"39","author":"Lim","year":"2007","journal-title":"Exp. Mol. Med."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/4\/244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:08:38Z","timestamp":1760029718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/4\/244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,2]]},"references-count":114,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["metabo15040244"],"URL":"https:\/\/doi.org\/10.3390\/metabo15040244","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,2]]}}}