Polyphenols-rich extract from Araucaria angustifolia: Differential mechanisms on cancer and normal cells

Cancer cells present differential metabolism compared to normal cells. Multiple molecular mechanisms converge to alter cellular metabolism, and some of these include a process of metabolic reprogramming which provides advantages to tumor cells in energy generation, growth and proliferation. Tumor energy production is basically dependent on glucose driven to glycolysis (Warburg effect), but it also happens by means of fatty acids and glutamine metabolism. Among the current challenges in cancer therapy, the tumor cell resistance and the absence of selectivity of anti-cancer agents stand out. It has been already shown that polyphenols are able to exert differential effects on normal and tumor cells. However, the exact mechanisms of these actions are not fully understood. In our previous study, we showed that a polyphenols-rich extract (PE) from Araucaria angustifolia held a selective capacity to inhibit the proliferation of human larynx HEp-2 cancer cells with minimal cytotoxicity to normal epithelial cells. We hypothesized that the effect presented by PE have happened by reversing the “Warburg effect” on cancer cells and inhibiting the mitochondrial electron transport chain complex I activity along with ATP depletion on these cells. In this research highlight we will discuss the effects of the PE on mitochondrial metabolism and their possible role in the modulation of mitochondrial sirtuin 3 (SIRT3) on tumor (HEp-2) and normal (HEK-293) cells, which may help to clarify the tumor selectivity exhibited by polyphenols.