Journal: Molecular Medicine Reports

Article Title: Schisantherin A induces ferroptosis in non-small cell lung cancer through activation of the YAP/ACSL4/TfR signaling pathway

doi: 10.3892/mmr.2025.13734

Figure Lengend Snippet: Sch A induces cell death and cell cycle arrest in A549 and HCC827 cells. Sch A considerably increased the death of (A) A549 and (B) HCC827 cells in comparison with the control group, according to flow cytometric analysis. Compared with Con, (C) A549 and (D) HCC827 cells presented a significant decrease in the number of G 2 + S-phase cells and a significant increase in the number of G 1 -phase cells. Fer-1 and DFO were able to significantly reverse the Sch A-induced decrease in (E) A549 and (F) HCC827 cell viability, according to the results of the Cell Counting Kit-8 analysis. *P<0.05, **P<0.01 and ***P<0.001 vs. Con; ## P<0.01 and ### P<0.001 vs. Sch A. DFO, deferoxamine; Con, control; Sch A, Schisantherin A; Fer-1, ferrostatin-1; Nec-1, necrostatin-1; 3-MA, 3-methyladenine.

Article Snippet: The following inhibitors were co-incubated with Sch A: Z-VAD-FMK (pan-caspase inhibitor; HY-16658B; final concentration: 20 μM); 3-Methyladenine (3-MA) (autophagy inhibitor, HY-19312; final concentration: 5 mM); Necrostatin-1 (Nec-1) (necroptosis inhibitor; MCE; HY-15760, 10 μM); Ferrostatin-1 (Fer-1) (ferroptosis inhibitor; MCE; HY-100579, 1 μM); Deferoxamine (DFO) (iron chelator/ferroptosis inhibitor; HY-B1625; all MCE; final concentration: 100 μM).

Techniques: Comparison, Control, Cell Counting

Journal: Molecular Medicine Reports

Article Title: Schisantherin A induces ferroptosis in non-small cell lung cancer through activation of the YAP/ACSL4/TfR signaling pathway

doi: 10.3892/mmr.2025.13734

Figure Lengend Snippet: In A549 and HCC827 cells, ferroptosis inhibitors prevent Sch A-induced apoptosis. Fer-1 and DFO were shown by JC-1 staining to reverse the Sch A-induced MMP reduction in (A) A549 and (B) HCC827 cells (scale bar, 30 µm). Fer-1 and DFO inhibited the Sch A-induced increase in MDA in (C) A549 and (D) HCC827 cells. Fer-1 and DFO counteracted the Sch A-induced reduction in GSH in (E) A549 and (F) HCC827 cells. Reverse transcription-quantitative PCR analysis revealed that Fer-1 and DFO reversed the Sch A-induced increase in Chac1 and ptgs2 levels in (G) A549 and (H) HCC827 cells. *P<0.05, **P<0.01 and ***P<0.001 vs. Con; # P<0.05, ## P<0.01 and ### P<0.001 vs. Sch A. Con, control; Chac1, glutathione-specific γ-glutamylcyclotransferase 1; ptgs2, prostaglandin-endoperoxide synthase 2; Fer-1, ferrostatin-1; DFO, deferoxamine; Sch A, Schisantherin A; MDA, malondialdehyde; GSH, glutathione.

Article Snippet: The following inhibitors were co-incubated with Sch A: Z-VAD-FMK (pan-caspase inhibitor; HY-16658B; final concentration: 20 μM); 3-Methyladenine (3-MA) (autophagy inhibitor, HY-19312; final concentration: 5 mM); Necrostatin-1 (Nec-1) (necroptosis inhibitor; MCE; HY-15760, 10 μM); Ferrostatin-1 (Fer-1) (ferroptosis inhibitor; MCE; HY-100579, 1 μM); Deferoxamine (DFO) (iron chelator/ferroptosis inhibitor; HY-B1625; all MCE; final concentration: 100 μM).

Techniques: Staining, Reverse Transcription, Real-time Polymerase Chain Reaction, Control

Journal: Advanced Healthcare Materials

Article Title: Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain

doi: 10.1002/adhm.202401629

Figure Lengend Snippet: Deferoxamine‐conjugated oxidized carbon nanozymes (DEF‐PEG‐cOACs) demonstrate iron chelation effect in bEnd.3 cells. Mouse brain endothelial (bEnd.3) cells were cultured in media with and without iron (III) chloride (50 µ m ), DEF‐PEG‐cOACs (4 µg mL −1 ), and the iron chelator deferoxamine (50 µ m ). Free deferoxamine was estimated as 100X higher molarity than when particle bound. Intracellular free iron was measured using fluorescence microscopy with FerroOrange, a fluorescent probe sensitive to unbound Fe 2+ . Treatment of iron cells with DEF‐PEG‐cOACs and deferoxamine in the presence of iron (III) chloride significantly decreases FerroOrange fluorescence, reflecting decreased intracellular free iron. DEF‐PEG‐cOACs are ≈63‐fold more potent per mole of deferoxamine than free deferoxamine. No significant difference in fluorescence between DEF‐PEG‐cOAC and deferoxamine‐treated cells was observed in the absence of media iron supplementation, suggesting that DEF‐PEG‐cOACs and deferoxamine do not significantly interfere with FerroOrange fluorescence. N = 3 technical replicates. One‐way ANOVA. * p < 0.05; ** p < 0.01; *** p < 0.001; “ns” indicates a non‐significant comparison.

Article Snippet: Murine brain endothelial (bEnd.3) cells were seeded onto a 24‐well plate at a density of 20 000 cells mL −1 and cultured overnight in the presence of 4 μg mL −1 DEF‐PEG‐cOACs or 50 μ m deferoxamine mesylate (Thermo Fisher Scientific, #461770010) at 37 °C with 5% CO 2 .

Techniques: Cell Culture, Fluorescence, Microscopy, Comparison

Journal: Advanced Healthcare Materials

Article Title: Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain

doi: 10.1002/adhm.202401629

Figure Lengend Snippet: Pro‐energetic effects of deferoxamine‐functionalized OCNs a) Synthesis schematic for PEGylated oxidized carbon nanozymes synthesized from coconut‐derived activated charcoal (PEG‐cOACs) and PEG‐cOACs functionalized with the iron chelator deferoxamine (DEF‐PEG‐cOACs). PEG‐cOACs and DEF‐PEG‐cOACs increase bEnd.3 cell b) oxygen consumption rates (OCR) and c) extracellular acidification rates (ECAR), indicative of pro‐aerobic and pro‐glycolytic shifts in energy metabolism respectively. Of note, the increase in OCR versus untreated (CTL) cells is greater with DEF‐PEG‐cOAC treatment, suggesting an improvement upon the pro‐aerobic shift facilitated by PEG‐cOACs. d) Higher OCR in PEG‐ and DEF‐PEG‐cOAC‐treated bEnd.3 cells after the addition of the ATP synthase inhibitor oligomycin (2 µ m ) suggests that the pro‐aerobic effects of PEG‐ and DEF‐PEG‐cOACs persist through negative stressors of mitochondrial respiration. e) Higher extracellular lactate release as a result of 24 h PEG‐cOAC and DEF‐PEG‐cOAC treatment of bEnd.3 cells support a pro‐glycolytic role for these OCNs at a comparable magnitude to that of PEG‐HCCs. Mean + SEM, one‐way ANOVA; * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Murine brain endothelial (bEnd.3) cells were seeded onto a 24‐well plate at a density of 20 000 cells mL −1 and cultured overnight in the presence of 4 μg mL −1 DEF‐PEG‐cOACs or 50 μ m deferoxamine mesylate (Thermo Fisher Scientific, #461770010) at 37 °C with 5% CO 2 .

Techniques: Synthesized, Derivative Assay

Journal: Advanced Healthcare Materials

Article Title: Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain

doi: 10.1002/adhm.202401629

Figure Lengend Snippet: Proposed schematic of pleiotropic OCN‐mediated protection during hemorrhagic traumatic brain injury (TBI). Disruption of cerebral vasculature as a result of injury results in extravascular leakage and pooling of blood. Iron released from the breakdown of hemoglobin in blood generates cytotoxic reactive oxygen species (ROS) via the Fenton reaction, exacerbating cellular injury and decreasing the efficiency of neuronal energy metabolism. Deferoxamine‐functionalized OCNs may mediate cell and tissue protection during hemorrhagic TBI by i): chelating free iron, thereby limiting ROS generation, ii): catalyzing the dismutation of ROS, iii): rescuing injury‐inhibited aerobic (mitochondrial) respiration, and iv): stimulating glycolytic energy metabolism in neurons, astrocytes and endothelial cells, thus ensuring the generation of lactate that is transported to neurons via the endothelial/astrocyte‐neuron lactate shunt and utilized as an important adjunct energy source for mitochondrial ATP and NAD+ generation.

Article Snippet: Murine brain endothelial (bEnd.3) cells were seeded onto a 24‐well plate at a density of 20 000 cells mL −1 and cultured overnight in the presence of 4 μg mL −1 DEF‐PEG‐cOACs or 50 μ m deferoxamine mesylate (Thermo Fisher Scientific, #461770010) at 37 °C with 5% CO 2 .

Techniques: Disruption

Journal: Free radical biology & medicine

Article Title: Acetyl-CoA carboxylase activation disrupts iron homeostasis to drive ferroptosis.

doi: 10.1016/j.freeradbiomed.2025.05.421

Figure Lengend Snippet: Fig. 8. Empagliflozin mitigates neuronal iron overload and ferroptosis via the ACC–NRF2–TFEB–lysosome pathway. a–c, Representative Western blot images and quantitative analysis showing the expression of p-ACC, NRF2, and TFEB in HT22 cells subjected to IH with or without empagliflozin (50 μM) treatment. d–e, PI staining (d) and FerroOrange staining (e) were performed in HT22 cells after IH exposure and treated with or without empagliflozin (50 μM) or DFO (100 μM). f–g, HT22 cells were transfected with siCON or siTfeb, treated with empagliflozin, and subjected to IH exposure. Cell death was assessed using PI staining (g), and intracellular Fe2+ levels were measured by FerroOrange staining (f). h, Representative Western blot images and quantitative analysis of NRF2 and TFEB protein levels relative to β-actin in HT22 cells subjected to IH and treated with empagliflozin (50 μM), in the presence or absence of ML385 (5 μM). i–j, AO staining (i) and FerroOrange staining (j) in HT22 cells infected with LV-NC or LV-Tfeb, subjected to IH and treated with empagliflozin (50 μM) and ML385 (5 μM). k–l, Representative Western blot images and quantification of p-ACC, ACC, NRF2, and TFEB protein levels in mouse hippocampal tissues. m, Representative traces and quantitative data of mice in the MWM test (n = 12). n, Spontaneous alternation behavior and representative traces in the Y-Maze test (n = 12). o, EPM test was performed to evaluate anxiety-like behavior in mice. Time spent in the open arm, closed arm, and the middle zone were recorded (n = 12). p, TST was used to assess depression-like behavior, with total immobility time recorded (n = 12). Scale bars in (d–g, i, j) represent 50 μm. All data are presented as mean ± SEM. All individual data points and P values are shown. Statistical comparisons were performed using two-tailed unpaired t-tests (f, g, h, i, j), one-way ANOVA with Tukey’s multiple comparisons test (a–e, k–p) and two-way ANOVA (m, right, latency in MWM). Abbreviations: IH, intermittent hypoxia; EMPA, empagliflozin; DFO, deferoxamine; AO, acridine orange; MWM, Morris water maze; EPM, elevated plus maze; TST, tail suspension test. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: According to the experimental design, the following compounds were added to the two-hit model and incubated for 8 h: ND646 (1 μM, S8377, Selleck, USA), Deferoxamine (DFO, 100 μM, S5742, Selleck, USA), Z-VAD-FMK (10 μM, S7023, Selleck, USA), LDC7559 (50 μM, S9622, Selleck, USA), Ferrostatin-1 (Fer-1, 5 μM, SML0583, Sigma, USA), RSL3 (1 μM, S8155, Selleck, USA), Vacuolin-1 (Vac-1, 1 μM, S6912, Selleck, USA), Mannose (Man, 50 mM, HY-N0379, MCE, USA), LLeucyl-L-Leucine methyl ester hydrobromide (LLOMe, 2 mM, HY129905A, MCE, USA), and empagliflozin (50 μM, S8022, Selleck, USA).

Techniques: Western Blot, Expressing, Staining, Transfection, Infection, Two Tailed Test, Suspension

Journal: iScience

Article Title: CircPOLA2 sensitizes non-small cell lung cancer cells to ferroptosis and suppresses tumorigenesis via the Merlin-YAP signaling pathway

doi: 10.1016/j.isci.2024.110832

Figure Lengend Snippet:

Article Snippet: Deferoxamine mesylate (DFO) , MCE , Cat#HY-B0988.

Techniques: Control, Virus, Recombinant, Magnetic Beads, Protease Inhibitor, Silver Staining, Multiple Displacement Amplification, Purification, Cell Viability Assay, CCK-8 Assay, In Vitro, Sequencing, Expressing, Plasmid Preparation, Cloning, Software

Journal: EMBO Molecular Medicine

Article Title: Oxidative stress enhances the therapeutic action of a respiratory inhibitor in MYC ‐driven lymphoma

doi: 10.15252/emmm.202216910

Figure Lengend Snippet: Viability of FL MycER and BaF MycER cells primed or not with 100 nM OHT and treated with 135 nM IACS‐010759 for 48 h and/or with ascorbate at the indicated concentration for 6 h. n = 3 biological replicates; error bars: SD. 405/488 nm fluorescence ratio from the cytoplasmic Grx1‐roGFP2 reporter in FL MycER cells treated with 400 μM ascorbate (Asc) for the indicated periods of time, either with IACS‐010759 (36 h, left) or without it (right). The same experiment with OHT‐primed cells is shown in Appendix Fig D. Cell viability of FL5.12 cells at the end of treatment (48 h IACS‐010759, 6 h Asc), in the presence or absence of 50 μM deferoxamine (DFX, added 1 h before Asc). n = 3 biological replicates; error bars: SD. Quantification of lipid peroxides in FL5.12 cells treated with 135 nM IACS‐010759 for 24 h and/or 400 μM Asc for 3 h. ** P ≤ 0.01; * P ≤ 0.05 (one‐way ANOVA). Each point in the graph is from an independent biological replicate and represents the average of thousands of events (single cells) in a distinct cell population, normalized to the untreated condition. Single‐cell measurement distributions from a representative experiment are provided in Appendix Fig F. Source data are available online for this figure.

Article Snippet: IACS‐010759 (from the Institute for Applied Cancer Science at MD Anderson; Molina et al , ) and 4‐hydroxytamoxifen (Merck Life Science, Darmstadt, Germany) were dissolved in DMSO and ethanol, respectively; sodium L‐ascorbate, N‐acetyl‐L‐cysteine (NAC), L‐buthionine sulfoximine, 6‐aminonicotinamide, deferoxamine mesylate (Merck Life Science), dehydroepiandrosterone (Cayman Chemical Co., Ann Arbor, MI, USA), and tigecycline (Carbosynth, Newbury, UK) were dissolved in water.

Techniques: Concentration Assay, Fluorescence