Skip to main content
. Author manuscript; available in PMC: 2019 Aug 6.
Published in final edited form as: Nature. 2019 Feb 6;566(7744):403–406. doi: 10.1038/s41586-019-0904-1

Figure 2. Sapienate synthesis via FADS2 causes independence from the known SCD-catalyzed fatty acid desaturation.

Figure 2

(a,b) Relative proliferation of MDA-MB-468 control (with or without sapienate) and FADS2 overexpression cells upon treatment 0.5 nM Merck Frosst Cpd 3j normalized to control (a: n=9; b: control n=10, overexpression n=12). Two-way ANOVA with Tukey’s multiple comparisons.

(c,d) Relative proliferation of HUH7 and A549 cells (with or without sapienate) upon FADS2 knockdown with(out) 2 nM Merck Frosst Cpd 3j normalized to control (c: control n=9; shFADS2-1 n=6; shFADS2-2 n=6; d: n=6). Two-way ANOVA with Tukey multiple comparisons (within different cell lines); one-way ANOVA with Dunnett’s multiple comparisons (across different cell lines). Only pair-wise comparisons are depicted.

(e,f) Representative images of hematoxylin and eosin stain and relative area of resected tumor nodules derived from HUH7 control (non-targeting shRNA) or FADS2 knockdown (shFADS2-2) orthotopic liver xenografts in mice treated with vehicle or Merck Frosst Cpd 3j (1.5 mg per kg twice daily per oral; p.o.; control+vehicle n=13; control+SCD inhibition n=12; shFADS2-2+vehicle n=12, shFADS2-2+SCD inhibition n=14 of one experiment). Masks in (e) show the tissue contour and indicating tumor (black), necrotic (grey) and liver (white) area. Scale bar represents 1,000 µm in all cases. Box blots in (f) show box extending from the 25th to 75th percentiles, whiskers indicating the minimum and maximum, and a line indicating the mean. One-way ANOVA with Tukey’s multiple comparisons.

Experiments were performed in low FBS (1%: HUH7; 0.5%: others) with treatment of 72 h. Error bars represent SD from mean of biological independent samples (in vitro) or animals (in vivo), unless stated otherwise.