Edit Target: 11
Metformin is a pleiotropic drug: attributed to its action on AMPK
Metformin directly inhibits Complex I of the electron transport chain (ETC) in mitochondria. This inhibition decreases mitochondrial ATP production and forces cells to rely more on glycolysis for energy.
Cancer cells, especially those with high energy demands, may be particularly sensitive to a drop in ATP levels. The inhibition of Complex I also increases the AMP/ATP ratio, setting the stage for the activation of downstream energy stress pathways.
AMPK activation results in the inhibition of the mammalian target of rapamycin (mTOR) pathway, a central regulator of protein synthesis and cellular growth. mTOR inhibition reduces cell proliferation and limits tissue growth, which can slow tumor progression.
Metformin reduces circulating insulin levels, which in turn can decrease the activation of the insulin and insulin-like growth factor-1 (IGF-1) receptor pathways.
ETC Inhibitors: Drugs that directly inhibit specific ETC complexes (e.g., Complex I inhibitors like metformin or phenformin) can increase electron leakage and ROS production.