Unravelling the Warburg effect: glycolytic inhibitors as promising agents in cancer therapy

• Autor(es): Cunha, Andrea ; Silva, Patrícia ; Rocha, Ana Catarina ; Queirós, Odília
• Data: 2023
• Origem: Scientific Letters
• Assunto(s): tumor microenvironment; tumor metabolism; Warburg effect; glycolytic inhibitors
• Tipo de Documento: Artigo científico
• Idioma: Inglês

Descrição

The study of metabolic changes in cancer cells and their influence on tumor progression is still a challenge in oncobiology. Cancer cells are characterized by their high rates of glycolysis, even in the presence of oxygen, a phenomenon described as the Warburg effect. The increased glycolytic flux induces extracellular space acidification and boosts the more aggressive characteristics of cancer cells. Since monocarboxylate transporters, namely MCT1 and MCT4, play a role in the determination of intracellular pH, by exporting the accumulated lactic acid, they are upregulated in glycolytic tumors. Metabolic reprogramming emerged as an essential factor for cell survival and proliferation, also contributing to changes in the surrounding microenvironment, which often lead to resistance to antitumor compounds. Therefore, the altered metabolism can be an excellent target for new therapies in the cancer field, namely through the use of glycolytic inhibitors, which can inhibit cell metabolism and modify tumor microenvironment. 3-Bromopyruvate, 2-deoxyglucose and sodium dichloroacetate are able to alter the energy metabolism of cancer cells, either by acting directly on glycolysis or by redirecting pyruvate from glycolysis to the oxidative pathway. Here, we analyze how these glycolytic inhibitors interfere with tumor cell metabolism and, therefore, their potential use for new cancer therapeutic approaches.