{"doi":"10.1159/000317519","title":"Impairment of Aerobic Glycolysis by Inhibitors of Lactic Dehydrogenase Hinders the Growth of Human Hepatocellular Carcinoma Cell Lines","abstract":"<i>Background/Aims:</i>By reducing the number of ATP molecules produced via aerobic glycolysis, the inhibition of lactic dehydrogenase (LDH) should hinder the growth of neoplastic cells without damaging the normal cells which do not rely on this metabolic pathway for their energetic needs. Here, we studied the effect of oxamic and tartronic acids, 2 inhibitors of LDH, on aerobic glycolysis and cell replication of HepG2 and PLC/PRF/5 cells, 2 lines from human hepatocellular carcinomas. <i>Methods:</i>Aerobic glycolysis was measured by calculating the amounts of lactic acid formed. The effect on replication was assessed by culturing the cells in both standard conditions and glucose-deprived medium, which was used to shut down aerobic glycolysis. <i>Results:</i> The oxamic and tartronic acids inhibited aerobic glycolysis, impaired the growth of both cell lines and also induced an increased expression of p53-upregulated modulator of apoptosis, a signal of cell death. A strong impairment of cell replication by oxamic acid was only found when the cells were cultured in the presence of glucose, indicating that it was for the most part owing to inhibition of aerobic glycolysis. <i>Conclusions:</i>Inhibition of aerobic glycolysis achieved by blocking LDH could be useful in the treatment of human hepatocellular carcinomas. Without interfering with glucose metabolism in normal cells, it could hinder cell growth by itself and could also enhance the chemotherapeutic index of associated anticancer agents by decreasing the levels of ATP selectively in neoplastic cells.","journal":"Pharmacology","year":2010,"id":47300,"datarank":2.4715239345386832,"base_score":4.127134385045092,"endowment":4.127134385045092,"self_citation_contribution":0.6190701577567639,"citation_network_contribution":1.8524537767819191,"self_endowment_contribution":0.6190701577567639,"citer_contribution":1.8524537767819191,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":56,"citers_with_citation_signal":50,"citers_with_endowment":50,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":218704,"name":"Marcella Manerba","orcid":null,"position":1,"is_corresponding":false},{"id":218705,"name":"Marina Vettraino","orcid":null,"position":2,"is_corresponding":false},{"id":218706,"name":"Giuseppina Di Stefano","orcid":null,"position":3,"is_corresponding":false},{"id":218703,"name":"Luigi Fiume","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Impairment of Aerobic Glycolysis by Inhibitors of Lactic Dehydrogenase Hinders the Growth of Human Hepatocellular Carcinoma Cell Lines","abstract":"<i>Background/Aims:</i>By reducing the number of ATP molecules produced via aerobic glycolysis, the inhibition of lactic dehydrogenase (LDH) should hinder the growth of neoplastic cells without damaging the normal cells which do not rely on this metabolic pathway for their energetic needs. Here, we studied the effect of oxamic and tartronic acids, 2 inhibitors of LDH, on aerobic glycolysis and cell replication of HepG2 and PLC/PRF/5 cells, 2 lines from human hepatocellular carcinomas. <i>Methods:</i>Aerobic glycolysis was measured by calculating the amounts of lactic acid formed. The effect on replication was assessed by culturing the cells in both standard conditions and glucose-deprived medium, which was used to shut down aerobic glycolysis. <i>Results:</i> The oxamic and tartronic acids inhibited aerobic glycolysis, impaired the growth of both cell lines and also induced an increased expression of p53-upregulated modulator of apoptosis, a signal of cell death. A strong impairment of cell replication by oxamic acid was only found when the cells were cultured in the presence of glucose, indicating that it was for the most part owing to inhibition of aerobic glycolysis. <i>Conclusions:</i>Inhibition of aerobic glycolysis achieved by blocking LDH could be useful in the treatment of human hepatocellular carcinomas. Without interfering with glucose metabolism in normal cells, it could hinder cell growth by itself and could also enhance the chemotherapeutic index of associated anticancer agents by decreasing the levels of ATP selectively in neoplastic cells.","is_dataset_classified":null,"base_score":4.127134385045092,"endowment":4.127134385045092,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20699632","pmcid":null,"openalex_id":"https://openalex.org/W2008713788","authors":[],"funders":[],"total_grants":0,"fwci":1.5293,"citation_percentile":0.83673272,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":3},{"year":2014,"count":2},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":7},{"year":2018,"count":5},{"year":2019,"count":4},{"year":2021,"count":7},{"year":2022,"count":9},{"year":2023,"count":2},{"year":2024,"count":3},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"closed","license":"https://www.karger.com/Services/SiteLicenses","oa_locations":[{"url":"https://www.karger.com/Article/Pdf/317519","host_type":"publisher"},{"url":"https://doi.org/10.1159/000317519","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20699632","host_type":"repository"},{"url":"http://hdl.handle.net/11585/91257","host_type":"repository"}],"fields_of_study":["Cancer, Hypoxia, and Metabolism","Cancer Research and Treatments","Cancer and biochemical research","Medicine","Biology","Adenosine Triphosphate","Antineoplastic Agents","Apoptosis","Apoptosis Regulatory Proteins","Carcinoma, Hepatocellular","Cell Line, Tumor","Cell Proliferation","Citric Acid Cycle","Enzyme Inhibitors","Glucose","Glycolysis","Hep G2 Cells","Humans","L-Lactate Dehydrogenase","Lactic Acid","Oxamic Acid","Oxygen Consumption","Proto-Oncogene Proteins","Tartronates","Up-Regulation"],"mesh_terms":["Adenosine Triphosphate","Antineoplastic Agents","Citric Acid Cycle","Enzyme Inhibitors","Glucose","Glycolysis","Carcinoma, Hepatocellular","Humans","L-Lactate Dehydrogenase","Oxamic Acid","Oxygen Consumption","Proto-Oncogene Proteins","Tartronates","Up-Regulation","Apoptosis","Lactic Acid","Cell Line, Tumor","Cell Proliferation","Apoptosis Regulatory Proteins","Hep G2 Cells"],"keywords":["Anaerobic glycolysis","Glycolysis","Cell","Cell culture","Cell growth","Biochemistry","Lactic acid","Metabolism","Biology","Apoptosis","Chemistry","Cell biology","Cancer research","Bacteria"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.21316208.v1","title":"Additional file 7 of Early effects of LPS-induced neuroinflammation on the rat hippocampal glycolytic pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.21316208","title":"Additional file 7 of Early effects of LPS-induced neuroinflammation on the rat hippocampal glycolytic pathway","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-18T14:43:23.260650Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}