{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:39:20Z","timestamp":1788817160160,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["Anillo Grant-ACT210097"],"award-info":[{"award-number":["Anillo Grant-ACT210097"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["FONDECYT-11201322"],"award-info":[{"award-number":["FONDECYT-11201322"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["FONDECYT-1241547"],"award-info":[{"award-number":["FONDECYT-1241547"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["FONDECYT-3210367"],"award-info":[{"award-number":["FONDECYT-3210367"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["FONDEQUIP EQM220164"],"award-info":[{"award-number":["FONDEQUIP EQM220164"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["VID-UChile UM-03\/22"],"award-info":[{"award-number":["VID-UChile UM-03\/22"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["UI-024\/20"],"award-info":[{"award-number":["UI-024\/20"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)-Chile","doi-asserted-by":"publisher","award":["#21241704"],"award-info":[{"award-number":["#21241704"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>While cytostatic chemotherapy targeting DNA is known to induce genotoxicity, leading to cell cycle arrest and cytokine secretion, the impact of these drugs on fibroblast\u2013epithelial cancer cell communication and metabolism remains understudied. Our research focused on human breast fibroblast RMF-621 exposed to nonlethal concentrations of cisplatin and doxorubicin, revealing reduced proliferation, diminished basal and maximal mitochondrial respirations, heightened mitochondrial ROS and lactate production, and elevated MCT4 protein levels. Interestingly, RMF-621 cells enhanced glucose uptake, promoting lactate export. Breast cancer cells MCF-7 exposed to conditioned media (CM) from drug-treated stromal RMF-621 cells increased MCT1 protein levels, lactate-driven mitochondrial respiration, and a significantly high mitochondrial spare capacity for lactate. These changes occurred alongside altered mitochondrial respiration, mitochondrial membrane potential, and superoxide levels. Furthermore, CM with doxorubicin and cisplatin increased migratory capacity in MCF-7 cells, which was inhibited by MCT1 (BAY-8002), glutamate dehydrogenase (EGCG), mitochondrial pyruvate carrier (UK5099), and complex I (rotenone) inhibitors. A similar behavior was observed in T47-D and ZR-75-1 breast cancer cells. This suggests that CM induces metabolic rewiring involving elevated lactate uptake to sustain mitochondrial bioenergetics during migration. Treatment with the mitochondrial-targeting antioxidant mitoTEMPO in RMF-621 and the addition of an anti-CCL2 antibody in the CM prevented the promigratory MCF-7 phenotype. Similar effects were observed in THP1 monocyte cells, where CM increased monocyte recruitment. We propose that nonlethal concentrations of DNA-damaging drugs induce changes in the cellular environment favoring a promalignant state dependent on mitochondrial bioenergetics.<\/jats:p>","DOI":"10.3390\/antiox13070801","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T04:23:43Z","timestamp":1719980623000},"page":"801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CCL2 and Lactate from Chemotherapeutics-Treated Fibroblasts Drive Malignant Traits by Metabolic Rewiring in Low-Migrating Breast Cancer Cell Lines"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6099-0311","authenticated-orcid":false,"given":"Maria Jesus","family":"Vera","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Biology, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago 7830490, Chile"},{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Ponce","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biology, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago 7830490, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8861-806X","authenticated-orcid":false,"given":"Cristopher","family":"Almarza","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"},{"name":"Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Science (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago 7810000, Chile"},{"name":"Network for Snake Venom Research and Drug Discovery, Santiago 7810000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"},{"name":"Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Science (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago 7810000, Chile"},{"name":"Network for Snake Venom Research and Drug Discovery, Santiago 7810000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Guajardo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"},{"name":"Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Science (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago 7810000, Chile"},{"name":"Network for Snake Venom Research and Drug Discovery, Santiago 7810000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-4474","authenticated-orcid":false,"given":"Karen","family":"Dubois-Camacho","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"},{"name":"Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Science (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago 7810000, Chile"},{"name":"Network for Snake Venom Research and Drug Discovery, Santiago 7810000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-9014","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Tobar","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biology, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago 7830490, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix A.","family":"Urra","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"},{"name":"Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Science (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago 7810000, Chile"},{"name":"Network for Snake Venom Research and Drug Discovery, Santiago 7810000, Chile"},{"name":"Interuniversity Center for Healthy Aging (CIES), Consortium of Universities of the State of Chile (CUECH), Santiago 8320216, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Martinez","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biology, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago 7830490, Chile"},{"name":"Interdisciplinary Group on Mitochondrial Targeting and Bioenergetics (MIBI), Talca 3480094, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12935-022-02599-7","article-title":"Cancer-associated fibroblasts and resistance to anticancer therapies: Status, mechanisms, and countermeasures","volume":"22","author":"Feng","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1038\/s41590-023-01675-y","article-title":"The immunometabolic ecosystem in cancer","volume":"24","author":"Bantug","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12943-023-01860-5","article-title":"Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: New opportunities in cancer immunotherapy and advances in clinical trials","volume":"22","author":"Zhang","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s12276-023-01013-0","article-title":"Cancer-associated fibroblasts: From basic science to anticancer therapy","volume":"55","author":"Yang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8322","DOI":"10.7150\/thno.62378","article-title":"Metabolic reprogramming of cancer-associated fibroblasts and its effect on cancer cell reprogramming","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Martinez, J., and Smith, P.C. (2021). The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression. Cells, 10.","DOI":"10.3390\/cells10051046"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zheng, J., and Hao, H. (2023). The importance of cancer-associated fibroblasts in targeted therapies and drug resistance in breast cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1333839"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/jcp.25398","article-title":"Modulation of Mammary Stromal Cell Lactate Dynamics by Ambient Glucose and Epithelial Factors","volume":"232","author":"Tobar","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.4161\/cc.9.17.12731","article-title":"Ketones and lactate \u201cfuel\u201d tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism","volume":"9","author":"Bonuccelli","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1038\/s41388-019-0805-7","article-title":"Cancer-associated fibroblasts promote prostate cancer malignancy via metabolic rewiring and mitochondrial transfer","volume":"38","author":"Ippolito","year":"2019","journal-title":"Oncogene"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rong, G., Kang, H., Wang, Y., Hai, T., and Sun, H. (2013). Candidate markers that associate with chemotherapy resistance in breast cancer through the study on Taxotere-induced damage to tumor microenvironment and gene expression profiling of carcinoma-associated fibroblasts (CAFs). PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070960"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s10863-013-9519-7","article-title":"Cancer cell bioenergetics and pH regulation influence breast cancer cell resistance to paclitaxel and doxorubicin","volume":"45","author":"Baltazar","year":"2013","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Reuvers, T.G.A., Kanaar, R., and Nonnekens, J. (2020). DNA Damage-Inducing Anticancer Therapies: From Global to Precision Damage. Cancers, 12.","DOI":"10.3390\/cancers12082098"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1126\/science.1074740","article-title":"Interfaces between the detection, signaling, and repair of DNA damage","volume":"297","author":"Rouse","year":"2002","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mar\u00e9chal, A., and Zou, L. (2013). DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a012716"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: From mechanisms to therapeutic opportunities","volume":"22","author":"Krizhanovsky","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ebiom.2019.02.025","article-title":"Oxidized ATM-mediated glycolysis enhancement in breast cancer-associated fibroblasts contributes to tumor invasion through lactate as metabolic coupling","volume":"41","author":"Sun","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100791","DOI":"10.1016\/j.neo.2022.100791","article-title":"Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2\/CCR2 signaling interactions with MET receptor tyrosine kinases","volume":"28","author":"Acevedo","year":"2022","journal-title":"Neoplasia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e121291","DOI":"10.1172\/jci.insight.121291","article-title":"PARP-1 controls NK cell recruitment to the site of viral infection","volume":"4","author":"Shou","year":"2019","journal-title":"JCI Insight"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15566","DOI":"10.1074\/jbc.M201266200","article-title":"Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate","volume":"277","author":"Pascolo","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.1073\/pnas.0401064101","article-title":"Reconstruction of functionally normal and malignant human breast tissues in mice","volume":"101","author":"Kuperwasser","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13190","DOI":"10.1038\/s41598-018-31367-9","article-title":"FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1\/AMPK\/\u03b21-integrin pathway","volume":"8","author":"Urra","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Monroy-C\u00e1rdenas, M., Andrades, V., Almarza, C., Vera, M.J., Mart\u00ednez, J., Pulgar, R., Amalraj, J., Araya-Maturana, R., and Urra, F.A. (2023). A New Quinone-Based Inhibitor of Mitochondrial Complex I in D-Conformation, Producing Invasion Reduction and Sensitization to Venetoclax in Breast Cancer Cells. Antioxidants, 12.","DOI":"10.3390\/antiox12081597"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115344","DOI":"10.1016\/j.jep.2022.115344","article-title":"A paraguayan toad Rhinella schneideri preparation based on Mbya tradition increases mitochondrial bioenergetics with migrastatic effects dependent on AMPK in breast cancer cells","volume":"294","author":"Palominos","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"C\u00f3rdova-Delgado, M., Fuentes-Retamal, S., Palominos, C., L\u00f3pez-Torres, C., Guzm\u00e1n-Rivera, D., Ram\u00edrez-Rodr\u00edguez, O., Araya-Maturana, R., and Urra, F.A. (2021). FRI-1 Is an Anti-Cancer Isoquinolinequinone That Inhibits the Mitochondrial Bioenergetics and Blocks Metabolic Shifts by Redox Disruption in Breast Cancer Cells. Antioxidants, 10.","DOI":"10.3390\/antiox10101618"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.ijbiomac.2022.03.111","article-title":"Vivas-Ruiz, Functional, immunological characterization, and anticancer activity of BaMtx: A new Lys49- PLA(2) homologue isolated from the venom of Peruvian Bothrops atrox snake (Serpentes: Viperidae)","volume":"206","author":"Urra","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Olivares-Morales, M.J., De La Fuente, M.K., Dubois-Camacho, K., Parada, D., Diaz-Jim\u00e9nez, D., Torres-Riquelme, A., Xu, X., Chamorro-Veloso, N., Naves, R., and Gonzalez, M.J. (2018). Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn\u2019s Disease-Associated Adherent-Invasive Escherichia coli. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01026"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13672","DOI":"10.1038\/s41598-018-31939-9","article-title":"Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells","volume":"8","author":"Karabekmez","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/bj3500219","article-title":"The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells","volume":"350","author":"Dimmer","year":"2000","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1515\/hsz-2012-0198","article-title":"Integration of cellular bioenergetics with mitochondrial quality control and autophagy","volume":"393","author":"Hill","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20208","DOI":"10.1074\/jbc.M117.809012","article-title":"Lactate-mediated mitoribosomal defects impair mitochondrial oxidative phosphorylation and promote hepatoma cell invasiveness","volume":"292","author":"Lee","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.bbrc.2016.07.071","article-title":"Mitochondria-targeted antioxidant mitotempo protects mitochondrial function against amyloid beta toxicity in primary cultured mouse neurons","volume":"478","author":"Hu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1158\/1535-7163.MCT-17-1253","article-title":"Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY-8002 and Associated Markers of Resistance","volume":"17","author":"Quanz","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Lv, H., Li, H., Li, J., Yan, Y., Liu, F., Hao, W., Zhou, Z., Wang, P., and Zhou, S. (2021). Nitroreductase Increases Menadione-Mediated Oxidative Stress in Aspergillus nidulans. Appl. Environ. Microbiol., 87.","DOI":"10.1128\/AEM.01758-21"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.freeradbiomed.2010.09.021","article-title":"Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis","volume":"49","author":"Loor","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0003-9861(68)90193-8","article-title":"Effect of menadione on the electron transport pathway of yeast mitochondria","volume":"127","author":"Nosoh","year":"1968","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41419-019-1877-6","article-title":"Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling","volume":"10","author":"Tauffenberger","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"de la Cruz-L\u00f3pez, K.G., Castro-Mu\u00f1oz, L.J., Reyes-Hern\u00e1ndez, D.O., Garc\u00eda-Carranc\u00e1, A., and Manzo-Merino, J. (2019). Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01143"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1080\/15384101.2015.1120930","article-title":"Lactate promotes glutamine uptake and metabolism in oxidative cancer cells","volume":"15","author":"Dadhich","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ammarah, U., Pereira-Nunes, A., Delfini, M., and Mazzone, M. (Mol. Oncol., 2024). From monocyte-derived macrophages to resident macrophages\u2014How metabolism leads their way in cancer, Mol. Oncol., online ahead of print.","DOI":"10.1002\/1878-0261.13618"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1053\/j.seminoncol.2014.03.007","article-title":"Tumor microenvironment: Introduction","volume":"41","author":"Lisanti","year":"2014","journal-title":"Semin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1158\/2159-8290.CD-12-0345","article-title":"Cancer cell metabolism: One hallmark, many faces","volume":"2","author":"Cantor","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrc.2015.2","article-title":"DNA damage and the balance between survival and death in cancer biology","volume":"16","author":"Roos","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41584-022-00905-1","article-title":"Inflammation and DNA damage: Cause, effect or both","volume":"19","author":"Pezone","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.semcancer.2022.11.007","article-title":"Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics","volume":"87","author":"Sharma","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jiang, J., Huang, D., Jiang, Y., Hou, J., Tian, M., Li, J., Sun, L., Zhang, Y., Zhang, T., and Li, Z. (2021). Lactate Modulates Cellular Metabolism Through Histone Lactylation-Mediated Gene Expression in Non-Small Cell Lung Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.647559"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kumar, R., Mishra, A., Gautam, P., Feroz, Z., Vijayaraghavalu, S., Likos, E.M., Shukla, G.C., and Kumar, M. (2022). Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy. Cancers, 14.","DOI":"10.3390\/cancers14215268"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Deng, J., and Liao, X. (2023). Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer. BMC Med. Genom., 16.","DOI":"10.1186\/s12920-023-01726-1"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41571-022-00686-2","article-title":"The multiple roles of LDH in cancer","volume":"19","author":"Claps","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s42255-024-00994-0","article-title":"PMF-seq: A highly scalable screening strategy for linking genetics to mitochondrial bioenergetics","volume":"6","author":"To","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41573-021-00339-6","article-title":"Targeting cancer metabolism in the era of precision oncology","volume":"21","author":"Stine","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.07.006","article-title":"Monocarboxylate transporters in cancer","volume":"33","author":"Payen","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.drudis.2021.01.003","article-title":"Recent developments of human monocarboxylate transporter (hMCT) inhibitors as anticancer agents","volume":"26","author":"Wu","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7211","DOI":"10.1002\/jcp.30375","article-title":"The molecular structure and role of CCL2 (MCP-1) and C-C chemokine receptor CCR2 in skeletal biology and diseases","volume":"236","author":"Zhu","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41419-022-05169-x","article-title":"Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Vera, M.J., Guajardo, F., Urra, F.A., Tobar, N., and Mart\u00ednez, J. (2023). TNF-Alpha Promotes an Inflammatory Mammary Microenvironment That Favors Macrophage and Epithelial Migration in a CCL2- and Mitochondrial-ROS-Dependent Manner. Antioxidants, 12.","DOI":"10.3390\/antiox12040813"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jconrel.2017.03.013","article-title":"Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy","volume":"253","author":"Silva","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to Virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Akhter, N., Wilson, A., Thomas, R., Al-Rashed, F., Kochumon, S., Al-Roub, A., Arefanian, H., Al-Madhoun, A., Al-Mulla, F., and Ahmad, R. (2021). ROS\/TNF-\u03b1 Crosstalk Triggers the Expression of IL-8 and MCP-1 in Human Monocytic THP-1 Cells via the NF-\u03baB and ERK1\/2 Mediated Signaling. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910519"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1101\/gad.279737.116","article-title":"Carcinoma-associated fibroblasts: Orchestrating the composition of malignancy","volume":"30","author":"Gascard","year":"2016","journal-title":"Genes Dev."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/7\/801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:52Z","timestamp":1760108932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/7\/801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["antiox13070801"],"URL":"https:\/\/doi.org\/10.3390\/antiox13070801","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]}}}