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. Author manuscript; available in PMC: 2018 Jul 10.
Published in final edited form as: Nature. 2018 Jan 10;553(7688):351–355. doi: 10.1038/nature25170

Figure 1. SR9009 is selectively lethal in cancer cell lines driven by different oncogenic signaling.

Figure 1

a, SR9009 treatment is specifically cytotoxic in cancer cells (72h, one-way ANOVA, n=biological replicates, astrocytes (n=12 mock), (12 2.5µM),(12 5µM), (15 10µM), (18 20µM), P=ns, astrocytoma (n=8 mock), (n=9 2.5µM), (n=10 5µM), (n=11 10µM), (n=6 20µM), *P=0.037, BTICs (n=10 mock), (n=9 2.5µM), (n=9 5µM), (n=15 10µM), (n=18 20µM), ****P<0.0001. b, SR9009 treatment impairs viability of BJ-ELR, but not BJ cells (20µM, 7 days); c REV-ERBs expression levels in BJ and BJ-ELR; (qRT-PCR n=3 biological independent samples, two-tailed Mann–Whitney test P=ns). d, Jurkat cells are affected by SR9009 (n=12 biological replicates 72h 20µM, Mann–Whitney test, one-tailed ****P< 0.0001). e–f, Immunostaining for cleaved caspase 3/TUNEL (72h, 20uM); Quantification in f; n=5 (mock) n=6 (SR9009) biological independent samples, Mann–Whitney test, one-tailed cleaved Caspase 3 **P=0.0022; Tunel **P=0.0022. g, MCF-7 viability is affected by SR9009 (n=12 mock, n=8 SR9009 biological replicates 72h 20µM, Mann–Whitney test one-tailed ****P<0.0001). h–i, Immunostaining for cleaved caspase 3/TUNEL (72h, 20uM). Quantification in i (n=5 biological independent samples Mann–Whitney test one-tailed, cleaved Caspase 3 **P=0.004; Tunel **P=0.004). j HCT116 viability is affected by SR9009 (n=8 biological replicates, WST-1 assay, 72h, Mann–Whitney test, one-tailed ****P< 0.0001. k–l, Induction of apoptosis is showed by cleaved Caspase 3/TUNEL staining (72h, 20µM); Quantification on panel l; n=8 (mock) n=5 (SR9009) biological independent samples, Mann–Whitney test one-tailed cleaved Caspase 3 ***P=0.0008; TUNEL assay **P=0.0021. m–o Prolonged SR9009 treatment eradicates cancer cells (7 days, 20µM), while does not affect REV-ERBα/β shRNA expressing cells; p, REV-ERBα and REV-ERBβ qRT-PCR; n=4 biological independent samples; Mann–Whitney test one-tailed *P=0.0286. NS= not significant. a.u= arbitrary unit. Scale bars 50 µm. All panels three biological independent experiments, mean ± s.e.m. except c (mean ± s.d.).