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Fig. 4 | Cancer & Metabolism

Fig. 4

From: Bortezomib resistance in multiple myeloma is associated with increased serine synthesis

Fig. 4

Bortezomib resistant cells have a higher activity of the serine synthesis pathway. a, b Intra- and extracellular analysis of serine levels of RPMI-8226 wild type (WT) and bortezomib resistant (BTZ/100) cells. Cells were suspended in DMEM containing 8 mM [U-13C] D-glucose. Intracellular metabolites were extracted after 4, 8 and 24 h and analyzed by LC-MS (a). Data are means ± SD (n = 3) of unlabeled (white) and 13C- labeled serine (left panel). Labeled serine was plotted as M+1, M+2 and M+3 isotopomers (right panel). Media samples were collected after 8 and 24 h, followed by LC-MS analysis of extracellular serine (b). Results represent % peak area ± SD compared to non-treated media (n = 3). c Intracellular metabolite analysis of RPMI-8226 WT and BTZ/100 cells in the presence or absence of extracellular serine and glycine (−SG). Cells were grown complete medium in the presence or absence of 0.4 mM serine. After 24 h, media were replaced with matched media containing 20 mM [U-13C] D-glucose and intracellular metabolites were extracted after 4 h, followed by LC-MS analysis. Data are means ± SD (n = 3) of labeled metabolites. d Cell viability of RPMI-8226 WT and BTZ/100 cells after 48 h of serine starvation (−SG). Results represent mean cell viability ± SD compared to non-treated control (n = 3). e Cell viability of RPMI-8226 WT cells after 48 h in 0.4 mM, 0.1 mM or no serine, including 24 h of 10 nM bortezomib. Results represent mean cell viability ± SD compared to non-treated control (n = 3). One-way ANOVA tests were performed (ns = not significant, * = p < 0.05, ** = p < 0.01, **** = p < 0.0001). BTZ = bortezomib, GSH = glutathione

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