{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:18:07Z","timestamp":1791908287616,"version":"4.3.4"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center of Poland","doi-asserted-by":"publisher","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Center of Poland","doi-asserted-by":"publisher","award":["24444"],"award-info":[{"award-number":["24444"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Law Offices of Peter G. Angelos Grant","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}]},{"name":"Law Offices of Peter G. Angelos Grant","award":["24444"],"award-info":[{"award-number":["24444"]}]},{"name":"Mesothelioma Applied Research Foundation (MARF)","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}]},{"name":"Mesothelioma Applied Research Foundation (MARF)","award":["24444"],"award-info":[{"award-number":["24444"]}]},{"name":"Purine and Pyrimidine Society (MAF)","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}]},{"name":"Purine and Pyrimidine Society (MAF)","award":["24444"],"award-info":[{"award-number":["24444"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["2018\/31\/B\/NZ7\/02909"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/02909"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["24444"],"award-info":[{"award-number":["24444"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. The prognostic role of key effectors of glycolytic metabolism in MM prompted our studies on the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP\/NAD+ metabolism, glycolysis and mitochondrial respiration. The antiproliferative activity of GLUT-1 (PGL13, PGL14) and LDH-A (NHI-1, NHI-2) inhibitors, alone and in combination, were tested with the sulforhodamine-B assay in peritoneal (MESO-II, STO) and pleural (NCI-H2052 and NCI-H28) MM and non-cancerous (HMEC-1) cells. Effects on energy metabolism were measured by both analysis of nucleotides using RP-HPLC and evaluation of glycolysis and respiration parameters using a Seahorse Analyzer system. All compounds reduced the growth of MM cells in the \u00b5molar range. Interestingly, in H2052 cells, PGL14 decreased ATP concentration from 37 to 23 and NAD+ from 6.5 to 2.3 nmol\/mg protein. NHI-2 reduced the ATP\/ADP ratio by 76%. The metabolic effects of the inhibitors were stronger in pleural MM and in combination, while in HMEC-1 ATP reduction was 10% lower compared to that of the H2052 cells, and we observed a minor influence on mitochondrial respiration. To conclude, both inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were synergistic in the cells with the highest metabolic modulation. This underlines cellular energy metabolism as a potential target for combined treatments in selected cases of MM.<\/jats:p>","DOI":"10.3390\/ijms24097771","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T02:06:35Z","timestamp":1682388395000},"page":"7771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Metabolic Effects of New Glucose Transporter (GLUT-1) and Lactate Dehydrogenase-A (LDH-A) Inhibitors against Chemoresistant Malignant Mesothelioma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-4374","authenticated-orcid":false,"given":"Marika A.","family":"Franczak","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"},{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-0417","authenticated-orcid":false,"given":"Oliwia","family":"Krol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-7438","authenticated-orcid":false,"given":"Gabriela","family":"Harasim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8219-7497","authenticated-orcid":false,"given":"Agata","family":"Jedrzejewska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-0890","authenticated-orcid":false,"given":"Nadia","family":"Zaffaroni","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-0722","authenticated-orcid":false,"given":"Carlotta","family":"Granchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-104X","authenticated-orcid":false,"given":"Filippo","family":"Minutolo","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-0962","authenticated-orcid":false,"given":"Amir","family":"Avan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad 91886-17871, Iran"},{"name":"Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad 91886-17871, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7565-7504","authenticated-orcid":false,"given":"Elisa","family":"Giovannetti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Fondazione Pisana per la Scienza, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-9414","authenticated-orcid":false,"given":"Ryszard T.","family":"Smolenski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-2877","authenticated-orcid":false,"given":"Godefridus J.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"},{"name":"Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mishra, D., and Banerjee, D. 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