Fig. 3
From: Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing
The primary site that at which metformin exerts its effects is the mitochondria. Metformin inhibits complex 1 in the respiratory chain and induces an elevation of AMP/ATP or ADP/ATP and subsequently activates AMPK. The indirect effects of metformin primarily rely on liver cells, where metformin decreases gluconeogenesis and fatty acid synthesis, thus influencing systemic metabolism. The direct effects of metabolism mainly involve the energy consumption of cancer cells