Fig. 9: Targetable ROS-scavenging mechanisms selectively sensitize human breast cancers to biguanide treatment. | Nature Communications

Fig. 9: Targetable ROS-scavenging mechanisms selectively sensitize human breast cancers to biguanide treatment.

From: STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer

Fig. 9

Most breast cancers are characterized by higher levels of oxidative phosphorylation and consequently increased mitochondrial membrane potential, in comparison to normal epithelial cells. Biguanides preferentially accumulate in cells with actively respiring mitochondria. Biguanide treatment as monotherapy inhibits complex I of the electron transport chain and OXPHOS leading to energetic stress. By inhibiting complex I, phenformin also increases mitochondrial superoxide generation. Combination therapy with phenformin and inhibiting tumor antioxidants, such as Nqo1 and glutathione, leads to oxidative stress in addition to energetic stress, and a potent tumoricidal response.

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