Cancer cells with defective ETC activity display resistance to the antiproliferative effects of metformin.

A. Proliferation of 143Bwt and 143Bcytb cells cultured in medium containing the indicated doses of metformin. Cell numbers were determined after 72 h of treatment, and are expressed relative to cell counts in control conditions (0 mM metformin). Each data point represents the mean ± SEM for each condition (n = 10). B. Proliferation of 143Bwt and 143Bcytb cells treated with control siRNA (CTL) or ACL-specific siRNA. Cell counts were determined after 48 h of culture in medium containing 10 mM metformin and expressed relative to cell counts in control conditions. The data represent the mean ± SEM for each condition (n = 10) and are representative of three independent experiments. C. U-[13C]-acetate-derived lipogenic acetyl-CoA in 143Bwt cells with or without 5 mM metformin treatment for 72 h. D. Proliferation of 143Bwt cells cultured in the absence or presence of 5 mM metformin under control (white) or acetate supplementation (black, 5 mM) conditions. Growth curves over time are shown. Each data point represents the mean ± SD for each condition (n = 10), and is representative of three independent experiments. Raw data for this figure can be found in S6 Data.