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Increased glycolysis provides <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>, reducing agents and substrates for macromolecular synthesis in intensely dividing cells. Therefore, inhibition of glycolysis is one strategy in anticancer therapy as well as in improved efficacy of conventional anticancer chemotherapeutic agents. One such agent is doxorubicin (DOX), but the mechanism of sensitization of tumor cells to DOX by inhibition of glycolysis has not been fully elucidated. As oxidative stress is an important phenomenon accompanying DOX action and antioxidant defense is closely related to energy metabolism, the aim of the study was the evaluation of oxidative stress markers and antioxidant abilities of cancer cells treated with DOX while glycolysis is inhibited. HepG2 cells were treated with DOX and one of three glycolysis inhibitors: 2\u2010deoxyglucose, dichloroacetate or 3\u2010promopyruvate. To evaluate the possible interaction mechanisms, we assessed <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of selected genes related to energy metabolism and antioxidant defense; oxidative stress markers; and reduced glutathione (<jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> levels. Additionally, glutamine consumption was measured. It was demonstrated that the chemotherapeutic agent and glycolysis inhibitors induced oxidative stress and associated damage in HepG2 cells. However, simultaneous treatment with both agents resulted in even greater lipid peroxidation and a significant reduction in <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> levels. Moreover, in the presence of the drug and an inhibitor, HepG2 cells had a reduced ability to take up glutamine. These results indicated that cells treated with DOX while glycolysis was inhibited had significantly reduced ability to produce <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> and antioxidant defenses.<\/jats:p>","DOI":"10.1002\/2211-5463.12628","type":"journal-article","created":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T16:53:36Z","timestamp":1553964816000},"page":"959-972","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Inhibition of glycolysis disrupts cellular antioxidant defense and sensitizes HepG2 cells to doxorubicin treatment"],"prefix":"10.1002","volume":"9","author":[{"given":"Agnieszka","family":"Korga","sequence":"first","affiliation":[{"name":"Independent Medical Biology Unit Medical University of Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ostrowska","sequence":"additional","affiliation":[{"name":"Department of 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