Aglycemia induces apoptosis under hypoxic conditions in A549 cells

• Published in: Cell biochemistry and function 2024-03, Vol.42 (2), p.e3983-n/a
• Main Authors: Öğünç Keçeci, Yüksel, İncesu, Zerrin
• Format: Article
• Language: English
• Subjects: Acid production; Apoptosis; Cancer; Cancer therapies; Caspase; Cytochrome c; Galactose; Glucose; Glycolysis; Hypoxia; Immunotherapy; Lactic acid; Lung carcinoma; Lung neoplasms; Membrane potential; Metabolism; Solid tumors
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.3983

Many of the cancer cells produce energy with accelerated glycolysis and perform lactic acid production even under normoxic conditions called the “Warburg effect”. Metabolism can directly or indirectly regulate the apoptotic mechanism so that cancer cells take advantage of reprogrammed metabolism to avoid apoptosis. The aim of this study is to examine the mechanism of apoptosis by incubating human lung carcinoma cells (A549) under different metabolic conditions in hypoxia or normoxia environments. A549 cells were incubated in the normoxic or hypoxic condition that contained 5 mM glucose (Glc 5), 25 mM glucose (Glc 25), or 10 mM galactose (OXPHOS/aglycemic), and the mechanism of apoptosis was investigated. In the hypoxia condition, the rate of early apoptosis in aglycemic OXPHOS cells was increased (15.5% ±7.1). In addition, the activity of caspase‐3 (6.1% ± 0.9), caspase‐9 (30.4% ± 0.9), and cytochrome c expression level increased; however, the mitochondrial membrane potential (51.9% ± 0.4) was found to be decreased. Changing the amount of oxygen in glycolytic cells had no effect on apoptosis. However, it has been determined that apoptosis is stimulated under hypoxia conditions in aglycemic cells in which galactose is used instead of glucose. Considering that the majority of cancer cells are hypoxic, these data are important in determining targets in therapeutic intervention. Significance statement Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo‐, radio‐, and immunotherapy. Metabolism can directly or indirectly regulate the apoptotic mechanism so that cancer cells take advantage of reprogrammed metabolism to avoid apoptosis. In this article, the link between metabolism and apoptosis pathway under hypoxic conditıon was evaluated in A549 cells.