He emphasises the need for further research in animal models to determine whether targeting metabolic pathways can enhance the anti-tumor effects of IFN-γ during immunotherapy, particularly for cancers that are difficult to treat. "The study is really a proof-of-concept at this point," says Professor Dipankar Nandi, the corresponding author. This finding was unexpected, as lactic acid is typically considered a metabolic waste product. In plants, ROS play a crucial role in abiotic and biotic stress sensing. Remarkably, the addition of potassium lactate proved to be a game-changer, significantly reducing the growth of even the non-responsive cancer cells. Reactive oxygen species (ROS) are key signalling molecules that enable cells to rapidly respond to different stimuli. Reactive oxygen species, in particular the hydroxyl radical, can react with all biological macromolecules (lipids, proteins, nucleic acids. To tackle this, the team experimented with various methods to induce lactic acid and NO production in these stubborn cells. The most well known is endothelium-dependent vasorelaxation, which is impaired by a loss of NO. Several assays have been developed in the last 30 years for ROS evaluation. In biological systems, an excessive amount of ROS can cause oxidative damage to biological macromolecules being involved in different diseases. (A) DNA damage can occur in the form of double stranded breaks as a result of ROS-induced conversion of guanine to 8-oxoguanine. Many functions of the endothelium are affected by ROS. Reactive oxygen species (ROS) are reactive compounds derived from oxygen. ![]() Thus, a balance between ROS production and their removal. ![]() They discovered that liver and kidney cancer cell lines ramped up their production of nitric oxide (NO) and lactic acid when activated by IFN-γ, resulting in toxic reactive oxygen species (ROS) that can lead to cell death.Ĭonversely, colon and skin cancer cell lines did not exhibit the same response, suggesting a potential resistance to immunotherapy. Reactive oxygen species (ROS) can cause damage to the basic building blocks of the cell including DNA, protein and lipids. ROS, especially H2O2, serve as a signal molecule through oxidative modification of signaling proteins. This observation led them to explore the metabolic processes behind this phenomenon. The researchers observed that upon treating cancer cells with IFN-γ, the cell growth medium turned yellow, indicating an acidic environment due to the release of lactic acid.
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