Journal: Redox Biology

Article Title: Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer

doi: 10.1016/j.redox.2026.104099

Figure Lengend Snippet: Pinostilbene, identified through screening as a natural STING agonist, activates the STING/TBK1/IRF3 pathway in NSCLC cells in a concentration-dependent manner. (A) H1299 cells transfected with an IFNB1 promoter-driven luciferase reporter were stimulated with STING agonists poly(I:C) (1 μg/mL) or poly(dA:dT) (1 μg/mL) for 24 h to assess activation (n = 4). (B) Screening of a natural product library using the assay in (A) (n = 3). (C–J) Western blot analysis of STING, TBK1, and IRF3 phosphorylation in H1299 (C–F) and A549 (G–J) cells treated with Pinostilbene for 24 h (n = 3). (K) Immunofluorescence of p -IRF3 nuclear translocation in H1299 cells (n = 3). Scale bars, 20 μm. (L–R) qPCR analysis of IFNB1 (L), IFIT1 (M), IFIT2 (N), ISG15 (O), CXCL10 (P), IFI44 (Q), and IFI44L (R) mRNA in H1299 cells (n = 3). β-Actin was used as a control. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Statistical significance was determined by one-way ANOVA followed by Tukey's test. * P < 0.05; ** P < 0.01; *** P < 0.001; ns, not significant.

Article Snippet: Phospho-STING (p-STING), phospho-TBK1 ( p -TBK1), phospho-IRF3 ( p -IRF3), LC3B, IRP1, and IRP2 antibodies were obtained from Cell Signaling Technology (CST, Danvers, MA, USA).

Techniques: Concentration Assay, Transfection, Luciferase, Activation Assay, Western Blot, Phospho-proteomics, Immunofluorescence, Translocation Assay, Control

Journal: Redox Biology

Article Title: Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer

doi: 10.1016/j.redox.2026.104099

Figure Lengend Snippet: Pinostilbene activates the STING/ferroptosis pathway to exert antitumor effects in vivo . Lewis lung carcinoma-bearing mice were administered Pinostilbene (10 mg/kg, i.p., every two days) or vehicle control for 24 days, during which tumor volume was measured every other day prior to euthanasia (n = 6). (A) Tumor growth curve (n = 6). (B) Excised tumors (n = 6). (C) Tumor weight (n = 6). (D) H&E staining of major organs (n = 3). Scale bars, 50 μm. (E–H) Western blot of p-STING (E, F), p -TBK1 (E, G), and p -IRF3 (E, H) in tumors (n = 3). (I–M) qPCR of IFNB1 (I), IFIT1 (J), ISG15 (K), USP18 (L), and CXCL10 (M) mRNA in tumors (n = 3). (N–Q) FTH1 expression by IHC (n = 5) and Western blot (n = 3). Scale bars, 100 μm. (R, S) 4-HNE levels by IHC (n = 5). Scale bars, 100 μm. (T, U) Ki67 IHC for proliferation (n = 5). Scale bars, 100 μm. (V–X) qPCR of IL-1β (V), IL-6 (W), and TNF-α (X) mRNA in tumors (n = 3). (Y) Representative images of immunofluorescence for CD8 + and CD4 + T cell infiltration (n = 3). Scale bars, 100 μm. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Significance was determined by Student's t -test. ** P < 0.01; *** P < 0.001.

Article Snippet: Phospho-STING (p-STING), phospho-TBK1 ( p -TBK1), phospho-IRF3 ( p -IRF3), LC3B, IRP1, and IRP2 antibodies were obtained from Cell Signaling Technology (CST, Danvers, MA, USA).

Techniques: In Vivo, Control, Staining, Western Blot, Expressing, Immunofluorescence

Journal: bioRxiv

Article Title: STING causes replication stress and nascent DNA degradation via SAMHD1

doi: 10.64898/2026.03.28.714577

Figure Lengend Snippet: ( A ) Western blot analysis of subcellular fractions from HDF treated for 6 days with doxycycline (Dox) to induce progerin expression, for 24 h with hydroxyurea (HU), or transfected with single-stranded DNA (ssDNA). Fraction markers include β-tubulin (cytoplasm), SEC61 (membrane), Lamin A (nucleus), and Histone H3 (chromatin). Note the increased presence of STING at nucleus and chromatin upon replication stress. Membranes imaged with prolonged exposure (high exposure) show a marked increase in signal intensity. ( B ) Immunofluorescence (IF) with STING antibody in HDF treated with vehicle, ssDNA, HU, Doxy (progerin), or dsDNA. ( C ) Quantification of cGAMP levels measured by ELISA in HDF treated as indicated. ( D ) IF with STING antibody and quantification of percentage of cells showing STING localization to the perinuclear compartment (PNC) upon different treatments. ( E ) IF with antibody recognizing phosphorylated STING on Ser366 and quantification of percentage of cells positive for S366 p-STING. ( F ) Immunoblot analysis of STING, GFP-progerin, and markers of activation of the canonical cGAS-STING pathway ( S366 p-STING, S386 p-IRF3, and S172 p-TBK1) following treatments. ( G ) Immunoblot analysis of STING pathway components and ISG proteins (STAT1, S727 p-STAT1, RIG-I, and ISG15) after indicated treatments.

Article Snippet: Primary antibodies used were β-tubulin (1:5000- Origene-AP31823PU-N), GAPDH (1:1000- Cell Signaling-2118), Lamina A (1:3000- Abcam-1791), Progerin (1:1000 Santa Cruz-81511), ISG15 (1:1000 Santa Cruz-166755), STING (1:1000-Cell Signaling-13647), S366 p-STING (1:1000- Cell Signaling- 50907), RIG-I (1:1000-Cell Signaling-3743S), S33-p-RPA (1:1000 Bethyl- PLA0070), SAMHD1 (1:1000- Cell Singaling-49158), λH2AX (1:1000- Cell Signaling- 2577).

Techniques: Western Blot, Expressing, Transfection, Membrane, Immunofluorescence, Enzyme-linked Immunosorbent Assay, Activation Assay