Small-molecule inhibitors of 6-phosphofructo-1-kinase simultaneously suppress lactate and superoxide generation in cancer cells
Fig 8
In the co-culture of tumorigenic Jurkat cells and activated T-cells, apoptosis is enhanced in the presence of PFK1 cmpd.
It is assumed that extracellular lactate in tumors triggers an acidosis that prevents the normal functioning of immune cells. Since PFK1 cmpds are thought to suppress lactate formation, acidosis may not be formed, so fully functional T cells could defeat cancer cells by apoptosis. Accordingly, increased late apoptosis was expected in a co-culture of activated T cells and tumorigenic Jurkat cells treated with PFK1 cmpds. In fact, after 18 hours of co-culture incubation with untreated cells (vehicle), only 18% (Q2-R2) of the cells were detected at the late apoptosis stage using a flow cytometer. However, in the cells treated with 10 µM cmpd No. 9 under identical environmental conditions, significantly higher proportions of cells were observed in the late apoptosis stage (Q2-R2). No. 9 (46.83%) or 10 µM of cmpd No. 30 (44.63%).