Journal: Nature cancer

Article Title: LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer.

doi: 10.1038/s43018-020-00168-3

Figure Lengend Snippet: Fig. 3 | Raf counteracts the therapeutic efficacy of LXR activation in HCC. a, Schematic outline of an LXR reporter assay in mouse or human HCC cells using a lentiviral vector encoding LXRE linked to GFP (p-LXRE-GFP). b, LXRE reporter assay in MycOE; NrasG12V; Cdkn2aARF–/– + p-LXRE-GFP cells that were treated for 3 d with DMSO, sorafenib, T0901317 or SR9238 (GFP measurements in individual cells, values represent the mean ± s.d., n = 3 independent experiments, statistical significance was calculated by two-tailed Student’s t test). c, Reporter assay to compare LXR activation by sorafenib and T0901317 in vivo. Quantification was performed of tumor sections stained for native GFP and native RFP after intrahepatic delivery of pT-CaM-LXRE-G, pT-CaRIN and pSB13 and treatment with carrier, sorafenib or T0901317 (3 d, values represent the mean ± s.d., n = 4 mice per group, statistical significance was calculated by two-tailed Student’s t test). d, Treatment of MycOE; NrasG12V; Cdkn2aARF–/– cells with sorafenib or T0901317 (quantification of viable cells by crystal violet staining, values represent mean ± s.d., n = 3 independent experiments, statistical significance was calculated by two-tailed Student’s t test). e, Treatment of MycOE; NrasG12V; Cdkn2aARF–/– cells with DMSO, BI-882370, sorafenib or sunitinib ± T0901317 (quantification of viable cells by crystal violet staining, values represent the mean ± s.d., n = 3 independent experiments, statistical significance was calculated by two-tailed Student’s t test). f, Schematic overview of treatment responses in HCC using either an LXR agonist or a Raf inhibitor alone or a combination of both compounds. Numerical source data are provided.

Article Snippet: If not otherwise stated, MycOE; NrasG12V; Cdkn2aARF–/– or MycOE; Akt1Myr; Cdkn2aARF–/– HCC cells were treated with 0.015 μM A939572 (Selleckchem), with 2 μM ABT-199 (Selleckchem), with 5 μM sorafenib (Selleckchem), SR9238 (Selleckchem), BI-882370 (Cayman Chemicals), sunitinib (Selleckchem), ND-630 (Selleckchem), LY-3009120 (Selleckchem), RAF-265 (Selleckchem), RAF-709 (Selleckchem), dabrafenib (Selleckchem), SB5900885 (Selleckchem), AZD-6244 (Selleckchem), PD0325901 (Selleckchem) or MG-132 or with 15 μM T0901317 (Selleckchem), 24(S)-HC (Sigma-Aldrich), GW3965 (Selleckchem) or LXR-623 (Selleckchem).

Techniques: Drug discovery, Activation Assay, Reporter Assay, Plasmid Preparation, Two Tailed Test, In Vivo, Staining

Journal: Translational Oncology

Article Title: The Role of Promyelocytic Leukemia Protein in Steatosis-Associated Hepatic Tumors Related to Chronic Hepatitis B virus Infection 1

doi: 10.1016/j.tranon.2018.03.013

Figure Lengend Snippet: Different gene expression profiles of HBsAg -transgenic mice in the presence or absence of PML during HCC development. Comparison of t ranscriptional profiling in the livers of wild-type , HBsAg tg/0 , PML −/− and PML −/- HBsAg tg/0 mice with different ages, sex and pathology. (A) Internal control. (B) Lipogenic genes. (C) Inflammation and apoptosis genes. Error bars indicate mean ± SEM from 3 independent experiments. Note that the up-regulation of Scd1 mRNA levels is in concordance with HCC development in PML −/- HBsAg tg/0 mice.

Article Snippet: The SCD1 inhibitor A939572 (Biofine) was dissolved in alkmulphor/EtOH/saline solution (1:1:18).

Techniques: Gene Expression, Transgenic Assay, Comparison, Control

Journal: Translational Oncology

Article Title: The Role of Promyelocytic Leukemia Protein in Steatosis-Associated Hepatic Tumors Related to Chronic Hepatitis B virus Infection 1

doi: 10.1016/j.tranon.2018.03.013

Figure Lengend Snippet: Correlation of liver pathology with gene expression toward hepatocarcinogenesis in the livers of wild-type , HBsAg tg/0 , PML −/− and PML −/- HBsAg tg/0 mice with different ages, sex and pathology. (A) Heat map demonstrating the cluster of differentially expressed genes related to lipid metabolism. Note that Scd1 , Fads1 and Fads2 are desaturases involved in fatty acid synthesis and that Nr5a2 regulates cholesterol transport, bile acid homeostasis and steroidogenesis . (B) Epigenetic methylation analysis represented by percentage of growth control genes in livers from the same mice in (A). Note that, in addition to enhanced adipogenesis, PML loss is associated with impairment of the cell cycle and mitochondrial function during HBsAg-induced hepatocarcinogenesis. NDUFA13 (also called GRIM-19 ), a subunit of the mitochondrial NADH dehydrogenase, functions in the transfer of electrons from NADH to the respiratory chain and as a tumor suppressor by binding to STAT3. CDKN1c (also called p57Kip2 ) encodes a strong inhibitor of G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. (C) Correlation of liver histology with immunohistochemistry of Scd1 protein expression in HBsAg -transgenic mice with or without PML loss. Note that PML loss induces severe steatosis with diffusely enhanced Scd1 expression and early-onset adipose-like HCC in HBsAg -transgenic mice. Squares represent in-situ zoomed regions.

Article Snippet: The SCD1 inhibitor A939572 (Biofine) was dissolved in alkmulphor/EtOH/saline solution (1:1:18).

Techniques: Gene Expression, Methylation, Control, Binding Assay, Immunohistochemistry, Expressing, Transgenic Assay, In Situ

Journal: Translational Oncology

Article Title: The Role of Promyelocytic Leukemia Protein in Steatosis-Associated Hepatic Tumors Related to Chronic Hepatitis B virus Infection 1

doi: 10.1016/j.tranon.2018.03.013

Figure Lengend Snippet: Scd1 is a metabolic therapeutic target for synthetic lethality in steatosis-associated hepatic tumors of HBsAg -transgenic mice with PML deficiency. Treatment with a small molecule Scd1 inhibitor, A939572, or solution control for HBsAg -transgenic mice with or without PML loss (n = 10–20 for each group). Representative images of gross livers and H&E histology are shown. (A) Ten-month-old PML −/- HBsAg tg/0 mice. Treatment was started when multiple early-onset adipose-like solid-form HCCs (arrows) were developing. Note that the Scd1 inhibitor regressed the HCCs by inducing necrosis of the fatty tumors and caused sinus ectasia with hemorrhage and cyst formation after resolution. (B) Twelve-month-old wild-type , PML −/− and PML +/+ HBsAg tg/0 mice. Note that the treatment induced no cytotoxicity in normal liver cells or dysplasia. (C) Eighteen-month-old PML +/+ HBsAg tg/0 mice. Note that the late-onset fatless or fat burnt-out angiogenic trabecular-type HCCs (broken circles) did not respond to the Scd1 inhibitor.

Article Snippet: The SCD1 inhibitor A939572 (Biofine) was dissolved in alkmulphor/EtOH/saline solution (1:1:18).

Techniques: Transgenic Assay, Control

Journal: Translational Oncology

Article Title: The Role of Promyelocytic Leukemia Protein in Steatosis-Associated Hepatic Tumors Related to Chronic Hepatitis B virus Infection 1

doi: 10.1016/j.tranon.2018.03.013

Figure Lengend Snippet: PML expression is inversely correlated with dynamic HBsAg levels in human chronic HBV-related pathogenesis. Representative H&E staining and immunostaining of PML (a regulator involved in DNA damage response and repair, cell death and survival, and fatty acid oxidation), HBsAg (an HBV component), Ki-67 (a cell proliferation marker) and/or Scd1 (a key enzyme in fatty acid synthesis) from a normal liver (A), acute HBV infection (B), a chronic HBV carrier (C), and an invasive HBV-related HCC (D). Clinically, chronic HBV pathogenesis can be subdivided into several phases: immune tolerance (high HBsAg levels), immune clearance (decreased HBsAg expression), immune escape (low HBsAg levels), and HCC formation (HBsAg loss). Note that nuclear PML immunoreactivity is strong in acute infection but suppressed in the early phase of chronic infection, which shows intensive cytoplasmic HBsAg staining. PML suppression is relieved upon clearance of HBsAg, indicating a reciprocal interaction between PML and HBsAg. PML restoration appears to correlate with gradually burnt-out steatosis during HCC development while HBsAg is lost. The simultaneously rising PML, Scd1 and Ki-67 immunoactivity in the invasive front of HBsAg-losing HCC cells reflects active fatty acid catabolism and anabolism coupled with cell proliferation. Zoomed regions indicated by arrows are shown in squares.

Article Snippet: The SCD1 inhibitor A939572 (Biofine) was dissolved in alkmulphor/EtOH/saline solution (1:1:18).

Techniques: Expressing, Staining, Immunostaining, Marker, Infection

Journal: bioRxiv

Article Title: Caging of membrane-to-cortex attachment proteins can trigger cellular symmetry breaking

doi: 10.1101/2024.10.14.618153

Figure Lengend Snippet: A) Mol% abundance of cholesterol in plasma membrane isolates upon 5 mM treatment with MβCD. B) Mol% of double bonds per lipid molecule before and after treatment with A939572 + BSA loaded with stearic acid (18:0). C) Representative confocal image of the basal membrane of a NIH3T3 fibroblast expressing the membrane marker CAAX-GFP before and after photobleaching. D) Recovery curves after photobleaching. E) Diffusion coefficient upon perturbation of lipid composition by MβCD or A939572 + BSA 18:0. F) Representative bright field images of NIH3T3 fibroblasts before and after addition of MβCD and A939572 + BSA 18:0 showing rounding up. G) Experimental setup for cortical stiffness measurements on micropatterned dishes by nano-indentation. H) Cortical stiffness measurements upon perturbation of lipid composition by MβCD or A939572. I-J) Representative images (I) and quantification of F-actin (J) in NIH3T3 fibroblasts in control and MβCD treated cells (N = 3 experiments, delipidated FBS (delFBS) = 67 cells and MβCD = 71 cells). Each dot represents one cell. In all other box plots dots represent the mean of multiple measurements of a single cell unless specified otherwise. Scale bars = 5 μm, a.u. = arbitrary units. Normality of data distribution was tested by Shapiro-Wilk test. Two-tailed t-test was used for normally distributed data. Otherwise, a non-parametric Wilcox test was used.

Article Snippet: To modify lipid composition, cells were treated with either A939572 (Merck, SML2356) to inhibit SCD1, or Methyl -β - cyclodextrin (MβCD, Merck, C4555) to deplete cholesterol.

Techniques: Membrane, Expressing, Marker, Diffusion-based Assay, Control, Two Tailed Test

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris

doi: 10.3389/fcimb.2024.1434939

Figure Lengend Snippet: Haploinsufficient profiling and RNA-seq assays uncover the Δ(9) fatty acid desaturase Ole1 as a potential target of SPB00525. (A) GO biological process term enrichment of C. albicans heterozygous mutants depleted or enriched upon exposure to SPB00525 in both SC and YPD media. (B) Graphical representation of results from the SPB00525-induced haploinsufficiency profiling. Mutants were plotted according to their fitness defect score from lowest to highest. The fitness scores reflect the differential abundance of each mutant strain in the SPB00525-treated condition relative to the DMSO control. (C, D) Comparison of HIP profiles in both SC and YPD growth media. Venn diagrams indicate shared depleted (C) and enriched (D) mutants in the presence of SPB00525 in SC and YPD media. SPB00525- enriched and depleted mutants were identified using a fitness score cutoff of 2.5 (Log 2 ) and a false discovery rate of 5%. (E) Validation of the SPB00525-induced haploinsufficiency assay. WT (CAI4) and heterozygous mutants ( ole1 , orf19.5285 and pep12 ) cells were grown in SC medium and exposed or not to 6 µg/ml SPB00525. Results represent growth inhibition (%) relative to the DMSO control. (F) Increased dosage of OLE1 and orf19.5285 led to decreased SPB00525 sensitivity of C. albicans . WT (WT-Cip-Act) and strains overexpressing both OLE1 and orf19.5285 were exposed to 15 and 30 µg/ml SPB00525 and OD 600 reading were acquired at 24h. (G, H) Transcriptomic analysis of C. albicans response to SPB00525. GO enrichment of upregulated (G) and downregulated (H) transcripts of C. albicans cells exposed to 6 µg/ml SPB00525 for 15 and 60 min. (I) Gene set enrichment analysis (GSEA) of the C. albicans SPB00525-modulated transcriptome at 15- and 60-min. NES (normalized enrichment score) and nominal q -value obtained from the GSEA are shown for each correlation. The complete GSEA correlations are listed in Supplementary Table S4 . False-Discovery Rate ( q -value) of 1%.

Article Snippet: The SPB00525 chemical analogs A939572 (MolPort-003-983-382), PluriSln1 (MolPort-000-564-458), MK-8245 (MolPort-023-293-543), HTS06170 (MolPort-002-901-421), HTS06154 (MolPort-002-901-407), HTS05029 (MolPort-002-901-093), HTS05668 (MolPort-002-901-311), G514 (MolPort-000-882-466) and new batches of SPB00525 (MolPort-002-923-508) were obtained from MolPort.

Techniques: RNA Sequencing, Mutagenesis, Control, Comparison, Biomarker Discovery, Inhibition

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris

doi: 10.3389/fcimb.2024.1434939

Figure Lengend Snippet: Library screen data, hit validation, and antifungal activity of SPB00525. (A) Screen of the yeast bioactive library against molecules with antifungal activity against C. auris . Relative inhibition of each compound tested at 100 µM was determined on C. auris 381 isolate grown at 30°C in SC medium for 24 h. (B) Chemical structure of the aryl-carbohydrazide hit SPB00525. (C) Dose-response assay of SPB00525 on C. auris . The C. auris 381 strain was grown in SC medium with different concentration of SPB00525 and OD reading was taken after 24h of incubation. Results represent growth inhibition (%) relative to the DMSO control. (D) Heat map representing the dose-response assay of SPB00525 on different azole resistant (R) and sensitive (S) clinical isolates of C. auris . The minimal inhibitory concentrations (MIC) were determined following Clinical and Laboratory Standards Institute (CLSI) recommendations using RPMI medium. (E) Heat map of the dose-response assay of SPB00525 on sensitive and, azole- (Flu R ) and caspofungin-resistant (Caspo R ) clinical isolates of C. albicans . (F) Time-kill curve showing the fungicidal activity of SPB00525 against both C. auris and C. albicans . C. auris 381 and C. albicans SC5314 strains were exposed to different concentrations (3-15 µg/ml) at 24h. CFUs were calculated as described in the method section.

Article Snippet: The SPB00525 chemical analogs A939572 (MolPort-003-983-382), PluriSln1 (MolPort-000-564-458), MK-8245 (MolPort-023-293-543), HTS06170 (MolPort-002-901-421), HTS06154 (MolPort-002-901-407), HTS05029 (MolPort-002-901-093), HTS05668 (MolPort-002-901-311), G514 (MolPort-000-882-466) and new batches of SPB00525 (MolPort-002-923-508) were obtained from MolPort.

Techniques: Biomarker Discovery, Activity Assay, Inhibition, Concentration Assay, Incubation, Control

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris

doi: 10.3389/fcimb.2024.1434939

Figure Lengend Snippet: Inhibition of Ole1 desaturase activity by SPB00525. (A) Desaturation of fatty acyl CoAs by fungal Δ(9) fatty acid desaturase. Ole1 converts CoA-linked saturated (palmitoyl-CoA and stearyl-CoA) to monounsaturated fatty acids of 16 (palmitoleic acid) or 18 (oleic acid) carbons in length. (B, C) SPB00525 inhibits fatty acid desaturation. SPB00525 reduced both C16 and C18 desaturation (B) . (C) Fatty acid desaturation index (unsaturated/saturated ratio) of C16, C18 and total fatty acid of C. albicans SC5314 strain exposed to 9 and 30 µg/ml SPB00525 for 2.5 hours. Data are average of five experiments, and error bars are SD. UFA: Unsaturated fatty acids; SFA: Saturated fatty acids. (D, E) Supplementation of exogenous unsaturated fatty acids alleviates growth inhibition by SPB00525. C. albicans SC5314 (D) and C. auris 381 (E) cells were exposed to SPB00525 in SC medium supplemented with either saturated (palmitic + stearic acids) or unsaturated (palmitoleic and oleic acids) fatty acid mixture. (F) OLE1 essentiality was reverted by supplementation of an equimolar mixture of palmitoleic and oleic acids. The conditional shut-off mutant strain of OLE1 ( ole1 /pTet- OLE1 ) was grown in SC medium with tetracycline (SC+tet) supplemented with saturated or unsaturated fatty acids. Cells were grown at 30°C, and OD 600 readings were taken every 15 min for 2 days.

Article Snippet: The SPB00525 chemical analogs A939572 (MolPort-003-983-382), PluriSln1 (MolPort-000-564-458), MK-8245 (MolPort-023-293-543), HTS06170 (MolPort-002-901-421), HTS06154 (MolPort-002-901-407), HTS05029 (MolPort-002-901-093), HTS05668 (MolPort-002-901-311), G514 (MolPort-000-882-466) and new batches of SPB00525 (MolPort-002-923-508) were obtained from MolPort.

Techniques: Inhibition, Activity Assay, Mutagenesis

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris

doi: 10.3389/fcimb.2024.1434939

Figure Lengend Snippet: HTS06170 chemical analog of SPB00525 exhibit potent antifungal activity in vitro . (A-F) Chemical structure of commercially available analogs of SPB00525. (G-I) Chemical structure of known human stearoyl-CoA desaturase 1 inhibitors. (J) Antifungal activity of SPB00525 analogs tested at 15 and 30 µg/ml. C. albicans SC5314 and C. auris 381 strains were grown in SC medium and exposed to the corresponding compound for 24h at 30°C. Data reported as percentage growth relative to the untreated condition (DMSO). (K) Dose-response assay of HTS06170 on C. albicans and C. auris . The C. auris 381 and the C. albicans SC5314 strains were grown in SC medium with different concentration of HTS06170 and OD reading was taken after 24h of incubation at 30°C. Results represent growth inhibition (%) relative to the DMSO control. MICs of HTS06170 are indicated in parentheses for each fungal strain.

Article Snippet: The SPB00525 chemical analogs A939572 (MolPort-003-983-382), PluriSln1 (MolPort-000-564-458), MK-8245 (MolPort-023-293-543), HTS06170 (MolPort-002-901-421), HTS06154 (MolPort-002-901-407), HTS05029 (MolPort-002-901-093), HTS05668 (MolPort-002-901-311), G514 (MolPort-000-882-466) and new batches of SPB00525 (MolPort-002-923-508) were obtained from MolPort.

Techniques: Activity Assay, In Vitro, Concentration Assay, Incubation, Inhibition, Control

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents against Candida auris

doi: 10.3389/fcimb.2024.1434939

Figure Lengend Snippet: SPB00525 and HTS06170 exhibit in vivo activity against C. albicans and C. auris . (A) SPB00525 and HTS06170 attenuate candidiasis in Galleria mellonella . Larvae were first injected with C. albicans SC5314 strain followed by a second injection of either DMSO, 15 µg/ml of SPB00525 or HTS06170 and survival was monitored at the indicated time for a period of 4 days. (B, C) SPB00525 and HTS06170 attenuate damage of enterocytes cells caused by C. albicans (B) and C. auris (C) . Damage of the human epithelial intestinal cells HT-29 infected by C. albicans SC5314 or C. auris 381 strain was assessed using LDH release assay. Cell damage was calculated as percentage of LDH activity of each treatment to that of the control experiment (HT-29 damaged by 1% Triton X-100). Results are represented as the mean of three independent replicates. (D) Evaluation of SPB00525 and HTS06170 cytotoxicity using the LDH release assay. HT-29 cells were exposed to 2x, 4x and 6x MIC C. albicans or 5x, 10x and 15x MIC C. auris of both SPB00525 and HTS06170 for 24h. (E) SPB00525 and HTS06170 inhibit biofilm formation. C. albicans SC5314 cell suspension was seeded into 96-well polystyrene plates and incubated at 37°C for 2 hours to initiate biofilm formation. Biofilms were then exposed or not to either SPB00525 or HTS06170 and incubated for 24 hours prior to biomass assessment using the crystal violet assay. Results are represented as the mean of six independent replicates. (F) SPB00525 and HTS06170 inhibit filamentation of C. albicans in response to different stimuli. C. albicans SC5315 yeast cells was grown under hyphae-promoting conditions (FBS and Spider, RPMI or Lee’s media) at 37°C for 6 hours in the absence or the presence of aryl-carbohydrazides. Filament lengths were measured for at least 100 cells using ImageJ software.

Article Snippet: The SPB00525 chemical analogs A939572 (MolPort-003-983-382), PluriSln1 (MolPort-000-564-458), MK-8245 (MolPort-023-293-543), HTS06170 (MolPort-002-901-421), HTS06154 (MolPort-002-901-407), HTS05029 (MolPort-002-901-093), HTS05668 (MolPort-002-901-311), G514 (MolPort-000-882-466) and new batches of SPB00525 (MolPort-002-923-508) were obtained from MolPort.

Techniques: In Vivo, Activity Assay, Injection, Infection, Lactate Dehydrogenase Assay, Control, Suspension, Incubation, Crystal Violet Assay, Software

Journal: Chemical research in toxicology

Article Title: Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1

doi: 10.1021/acs.chemrestox.9b00112

Figure Lengend Snippet: SCD1 was suppressed by elemicin (E) and 1′-hydroxyelemicin (E′). (A) Ratios of monounsaturated-LPCs to saturated-LPCs. (B) Relative mRNA expression of hepatic Scd1 gene by qPCR. (C) Western blot analysis of SCD1. *, p < 0.05, **, p < 0.01, ***, p < 0.001.

Article Snippet: SCD1 inhibitor A939572 was obtained from Bide Pharmatech Ltd. (Shanghai, China).

Techniques: Expressing, Western Blot

Journal: Chemical research in toxicology

Article Title: Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1

doi: 10.1021/acs.chemrestox.9b00112

Figure Lengend Snippet: SCD1 inhibitor A939572 exacerbated the toxicity of 1′-hydroxyelemicin (E′). (A) Western blot analysis of SCD1. (B) A939572 significantly elevated TG content in mouse plasma after 1′-hydroxyelemicin treatment. (C) A939572 significantly elevated TG content in mouse liver after 1′-hydroxyelemicin treatment. (D) A939572 reduced monounsaturated-LPCs contents in mouse plasma. (E) Ratios of monounsaturated-LPCs to saturated-LPCs were reduced by A939572. *, p < 0.05 as compared to E′C group, **, p < 0.01 as compared to E′C group, #, p < 0.05 as compared to E′, group, ##, p < 0.01 as compared to E′ group and ###, p < 0.001 as compared to E′ group.

Article Snippet: SCD1 inhibitor A939572 was obtained from Bide Pharmatech Ltd. (Shanghai, China).

Techniques: Western Blot, Clinical Proteomics

Journal: Antioxidants & Redox Signaling

Article Title: SLC25A22 as a Key Mitochondrial Transporter Against Ferroptosis by Producing Glutathione and Monounsaturated Fatty Acids

doi: 10.1089/ars.2022.0203

Figure Lengend Snippet: SLC25A22 upregulates the expression of SCD. (A) Analysis of SCD protein expression in indicated PDAC cells ( left ). Cell viability of indicated PDAC cells after treatment with RSL3 (1 μ M ) or erastin (20 μ M ) for 24 h ( right ). (B) Cell viability of indicated PDAC cells after treatment with RSL3 (1 μ M ) or erastin (20 μ M ) in the absence or presence of A939572 (5 μ M ) for 24 h. Data in (A, B) are presented as the mean ± SD of three technical replicates from one representative dataset of three independent experiments. Statistical significance was analyzed using two-way ANOVA with Dunnett's post hoc test. *p < 0.05.

Article Snippet: A939572 (T4515) was purchased from TOPSCIENCE.

Techniques: Expressing