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

<p><b>A.</b> Proliferation of 143B<i>wt</i> and 143B<i>cytb</i> 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 (<i>n</i> = 10). <b>B.</b> Proliferation of 143B<i>wt</i> and 143B<i>cytb</i> 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 (<i>n</i> = 10) and are representative of three independent experiments. <b>C.</b> U-[<sup>13</sup>C]-acetate-derived lipogenic acetyl-CoA in 143B<i>wt</i> cells with or without 5 mM metformin treatment for 72 h. <b>D.</b> Proliferation of 143B<i>wt</i> 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 (<i>n</i> = 10), and is representative of three independent experiments. Raw data for this figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002309#pbio.1002309.s006" target="_blank">S6 Data</a>.</p>