Highly active modified enzyme 6-phosphofructo-1-kinase (PFK1), causes deregulation of glycolysis and is the main metabolic engine of rapid growth of cancer cells. Excessive metabolite flow also results in abundant NADH formation in the cytosol that can contribute to the increased formation of reactive oxygen species, which cause mutations and altered cell signaling of cancer cells. We tested the effectiveness of thirty-three specific PFK1 inhibitors in reducing the formation of reactive oxygen species in cancer cells and then selected the most effective of them, with which we performed dose dependent tests. Tumorigenic cell lines Caco-2, Colo 289, MDA-MB-231 and Jurkat were used. We found different efficacies of selected PFK1 inhibitors in the tested cell lines. Increased NADH formation in cancer cells is reoxidized upon reduction of pyruvate to lactate that is secreted from cancer cells. Extracellular lactate causes acidification in tumors and is a major inhibitor of the effectiveness of immune cells against cancer. By co-culture of Jurkat tumorigenic cells and activated T lymphocytes, a higher percentage of apoptosis was measured on a flow cytometer in Jurkat tumorigenic cells treated with a concentration of 10 μM specific PFK1 inhibitor (I3, I23 and I29) compared to the control. The results suggest that treatment of cancer cells with selected PFK1 inhibitors allowed activated T lymphocytes to kill cancer cells more efficiently compared to untreated cancer cells. Effective tested PFK1 inhibitors should be used in further research, as they represent potential drugs for the treatment of diseases such as cancer.
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