Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?

Figure 1

Mechanisms of metformin action to inhibit cancer. Metformin disrupts circulating glucose and insulin levels and reduces inflammation. The organic cation transporter (OCT1) mediates the first step in metformin cellular response [51–53]. (1) Metformin activates the AMPK-P pathway through inhibition of Complex 1 of the mitochondrial respiratory chain [54, 55]. This leads to the inhibition of mTOR and thus loss of cell proliferation and inhibition of glucose synthesis [56–59]. (2) LKB1 may act as an intermediatory of AMPK activation [60, 61]. (3) Metformin blocks cAMP and PKA, which in turn antagonizes glucagon action [62]. (4) Metformin acts as an antifolate hindering DNA replication [63]. (5) Metformin induces an anti-inflammatory response via the Src-mediated NF-κΒ pathway [64]. (6) Metformin action is implicated in both AMPK dependent and independent inhibition of the angiogenesis process [65].