TP53 and cancer: We also examined whether phenformin, a more lipophilic biguanide, also exert its anti-proliferative effects on cancer cells through inhibition of complex I. Phenformin inhibited oxygen consumption in Control-HCT 116 p53−/− cells and saponin-permeabilized Control HCT 116 p53−/− cells at 100-fold lower concentration compared to metformin (Figure 3A,C).