Figure 1.

Proposed targets of the molecular mechanisms of metformin to reduce the proliferation and growth of thyroid cancer cells. Metformin acts mainly through nuclear stimulation of AMPK, which decreases the activation of TSC2 and the activation of mTOR, with the subsequent reduction in cyclin D1 and p70S6K/pS6 signaling, resulting in the inhibition of protein synthesis and cell cycle arrest. The blockade of IRS-1 phosphorylation decreases the signaling of the PI3K/AKT pathway, which also contributes to the reduction in mTOR pathway activation. Likewise, the direct effects of metformin on the mitochondria, by reducing Complex 1 or mGPDH, decreases energy production and cell stress and leads to cell apoptosis.