Figure 2.

Cancer metabolism at a glance, with experimental in vitro IC50 values for selected metabolic inhibitors. Glucose enters cells and undergoes glycolysis, converted into pyruvate. Cancer cells can divert up to 85% of pyruvate to lactate, regardless of the presence of oxygen (Warburg effect, yielding two net ATP); an estimated 10% of pyruvate goes towards biosynthesis and 5% to OXPHOS [56]. In normal, non-tumoral cells, the majority of pyruvate undergoes OXPHOS (30–32 ATP molecules). To decrease the Warburg effect and facilitate oxidative metabolic reprogramming, PDKs can be inhibited by dichloroacetate (DCA), supporting the entry of pyruvate in the mitochondria, and LDH can be targeted via sodium oxamate (SOD). “Glutamine addiction” can be regulated by glutaminase inhibitors such as 6-diazo-5-oxo-L-norleucine (DON) [57]. Lastly, metformin hydrochloride (MF) has pleiotropic effects: ETC complex I inhibition leads to downstream signaling via AMPK and mTOR [58]. In color-matching boxes, we display concentrations required for 50% viability inhibition (IC50) after 72 h of treatment. One-way ANOVA statistical significance of three biological experiments was calculated with normalized raw fluorometric data; p < 0.05 *; p < 0.01 **; p < 0.001 ***. Abbreviations: ETC (electron transport chain), mTOR (mammalian target of rapamycin), PDK (pyruvate dehydrogenase kinase), PDH (pyruvate dehydrogenase), GLS (glutaminase), LDH (lactate dehydrogenase), GLS (glutaminase), ECAR (extracellular acidification rate), OCR (oxygen consumption rate).