Metformin inhibits de novo palmitate synthesis in cancer cells.

<p>A–F. Palmitate biosynthesis in metformin-treated H1299 cells. Cells were cultured for 48 h with (+) or without (−) 5 mM metformin, followed by an additional 24 h of culture with U-[<sup>13</sup>C]-glucose or U-[<sup>13</sup>C]-glutamine. Relative lipogenic acetyl-CoA derived from labeled glucose (<b>A</b>) or labeled glutamine (<b>D</b>). U-[<sup>13</sup>C]-glucose-derived (<b>B</b>) or U-[<sup>13</sup>C]-glutamine-derived (<b>E</b>) palmitate was determined by GC-MS. Data are normalized to cell numbers. <b>C, F.</b> Mass isotopomer distribution of U-[<sup>13</sup>C]-glucose-derived (<b>C</b>) or U-[<sup>13</sup>C]-glutamine-derived (<b>F</b>) palmitate. <b>G.</b> Proliferation of H1299 NSCLC cells expressing control (CTL) or ATP citrate lyase (ACL)-specific siRNAs following culture for 72 h with (+) or without (−) 5 mM metformin. Cell numbers are expressed relative to cell counts in control conditions (0 mM metformin), and data represent the mean ± SEM for each condition (<i>n</i> = 20). Levels of ACL knockdown in H1299 cells were determined by immunoblot. *, <i>p</i> < 0.05; **, <i>p</i> < 0.01. 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.s004" target="_blank">S4 Data</a>.</p>