erastin

Mitophagy-deficient tumors lack this anti-ferroptotic mechanism, unleashing the generation of lipid peroxidation and potent ferroptotic cell death induced by erastin, RSL3, cysteine deprivation, radiotherapy, and immunotherapy. In summary, patient-derived organoids of colorectal cancer patients for screening ferroptosis-sensitive tumors are established, providing a paradigm for identifying that patient-derived tumors are sensitive to ferroptosis-inducing therapies. This study concludes that mitophagy-deficient tumors are vulnerable to ferroptosis induction, which may lead to the development of new therapeutic strategies for tumors deficient in mitophagy.

Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.

More recently, ferroptosis-a novel, non-apoptotic form of cell death-was identified in NRAS-mutant HT-1080 fibrosarcoma cells exposed to erastin and other NRLs...Overall, the published data support the idea that multi-layered endogenous antioxidant defense mechanisms in the liver limit the occurrence of pathophysiologically relevant LPO under normal conditions. Only when these defense mechanisms are severely compromised does ferroptosis become a significant mode of drug-induced cell death.

In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on...There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects.

ACSL4 level is significantly overexpressed in liver cancer. Erastin increases MDA contents and down-regulates ACSL4 expression, thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells, and these effects can be reversed by Fer-1.

Cells cultured in FBS containing higher selenium concentrations exhibited elevated GPx4 expression, and were resistant to ferroptosis induced by erastin and RSL3. These findings suggest that the variability of selenium content in different FBS batches can significantly influence the susceptibility of cells to ferroptosis, highlighting the importance of standardizing these factors to enhance the reproducibility of ferroptosis-related experiments.

Elevated CISD2 levels were found to be associated with decreased sensitivity of DLBCL patients to the R-CHOP regimen, as indicated by bioinformatics and clinical cohort analysis...Treatment of DLBCL cell lines with Erastin led to decreased CISD2 levels...Our findings suggest that CISD2 may play a role in the drug resistance observed in DLBCL patients. Inhibition of CISD2 could enhance ferroptosis and ferritinophagy, potentially improving the sensitivity of DLBCL cells to DOX treatment.

Here, we report that tumor cells that express PD-L1 are sensitive to ferroptosis inducers such as imidazole ketone erastin (IKE)...This ANC targets PD-L1-expressing cells in vitro and in vivo and induces ferroptosis, resulting in tumor suppression. Importantly, this approach is superior to systemic administration of IKE because it enables enhanced delivery of IKE specifically to tumor cells and it requires lower drug doses for efficacy.

Loss of PRDX6 resulted in increased sensitivity to erastin-induced ferroptosis, independent of selenium and GPX4, as a consequence of increased levels of lipid hydroperoxides, that reverted to normal levels upon rescue with PRDX6. The results presented demonstrate that all three enzymatic activities of PRDX6 contribute to the role of this multifunctional enzyme in diverse cellular processes, including membrane phospholipid remodeling and glycerophospholipid functional diversity, resulting in altered lipid peroxides and modulation of AA disposition and traffic. These contributions highlight the complexity of the changes that loss of PRDX6 exerts on cell functionality..

In this study, we found that down-regulation of BRIP1 could inhibit cell viability and proliferation in glioma cells through the induction of ferroptosis. This process was associated with increased oxidative stress, which was mediated by the down-regulation of SLC7A11 (xCT (Cysteine/glutamate transporter)) expression.

Interestingly, the combination treatment of Eto and IKE blocked MDSCs' immunosuppressive function and accumulation by downregulating the expression of SLC7A11, GPX4, and ARG1 while promoting T-cell proliferation and infiltration into tumor tissues to enhance cancer therapy. These data provide a rationale for the combination therapy of a specific CPT1A inhibitor, Eto, with IKE in clinical settings.

In this study, we proved that iberverin can induce intracellular reactive oxygen species (ROS) generation to inhibit cell proliferation and initiate ferroptotic cell death in HCC cells, which can be eradicated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) or deferoxamine mesylate (DFO) and ROS scavenger (GSH or NAC). Significantly, a low dose of iberverin can remarkably increase the sensitivity of HCC cells to ferroptosis induced by canonical ferroptosis inducers RSL3 and imidazole ketone erastin (IKE). This study uncovers a critical function of iberverin in preventing HCC through ferroptosis and provides a promising strategy for HCC treatment either via iberverin alone or in combination with canonical ferroptosis inducers in the future.

We also evaluated the susceptibility of MAZ-overexpressing OPCs to ferroptosis inducer, erastin, and demonstrated that MAZ-overexpressing OPCs were resistant to erastin-induced ferroptosis...Moreover, we elucidate the mechanism responsible for MAZ's protective effects on OPC death and differentiation, which may be achieved through transcriptional activation of SOX2. Our findings introduced MAZ as a beneficial modulator of OPC survival and differentiation, and it could serve as a potential therapeutic target for demyelination diseases.

By taking advantage of the sensitivity difference between tumor cells and dendritic cells (DCs) to the ferroptosis inducer erastin (Er) based on varying xCT expression levels, we developed Er-loaded nanoparticles CNP/Er. These nanoparticles not only enhance ferroptosis in 4T1 cells through Gpx4 inhibition by CNP but also promote DC maturation by utilizing CNP's hypoxia-responsive mechanism to increase ROS levels. The CNP/Er was believed to be an ideal candidate for bilateral regulation of ferroptosis and immune activation in one nanoreactor.

Additionally, knocking out ANP32E significantly enhanced EC cell sensitivity to PTX, Combining PTX with the ferroptosis inducer erastin was more effective in inhibiting tumor growth. In vivo, we confirmed the synergistic effect of ANP32E knock-out combined with PTX demonstrating superior tumor suppressing. Overall, our findings suggest that ANP32E regulates EC progression and ferroptosis through the p53/SLC7A11 axis, offering a potential molecular target for overcoming PTX resistance in EC treatment.

Additionally, Erastin depletes GSH by inhibiting the cystine/glutamate antiporter system, reducing cystine uptake and impairing GPX4, while also increasing intracellular H2O2 levels by activating NOX4 protein expression...Furthermore, this nanoplatform significantly inhibited tumor cell growth and extended the survival time of tumor-bearing mice in vivo. This engineered nanoplatform, which enhances ferroptosis through gas therapy, shows significant promise for ferroptosis-based cancer therapy and offers potential strategies for clinical tumor treatment.

CKS2 suppresses ferroptosis in CC by modulating GSH metabolism in both in vitro and in vivo settings. These findings offer new insights into targeting CKS2 for CC treatment and shed light on the mechanism of ferroptosis in CC.

STEAP3 serves as an independent biomarker for glioma prognosis with significant diagnostic value. High STEAP3 expression was correlated with poor overall outcomes of glioma patients. Knockdown of STEAP3 significantly suppressed the proliferation of glioma cells and increased erastin-induced ferroptosis via Nrf2/GPX4 pathway.

Together, our study identified HBX's role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients.

In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Inhibitors of ferroptosis include ferrostatin-1, liproxstatin-1, vitamin E and coenzyme Q10. By contrast, compounds such as erastin, RSL3 and FIN56 have been identified as inducers of ferroptosis...The present review focused on molecular targets such as p53 and ACSL4, the process of targeted medications in combination with PDT in CCA and the pathways of lipid peroxidation, the Xc-system and GSH-GPX4 in ferroptosis. The present review thus offered novel perspectives to improve the current understanding of CCA.

EC therapy activates the PERK-eIF2α-ATF4 signaling pathway to increase ER stress, thereby promoting ferroptosis in lung cancer cells and inhibiting the occurrence and development of lung cancer. Our research suggests that EC may become a drug candidate for treating lung cancer.

Our findings suggest that Erastin or Lenvatinib can enhance the induction of ferroptosis in cholangiocarcinoma cells by photodynamic therapy by increasing intracellular ROS and inhibiting intracellular antioxidant pathways.

Ferroptosis inhibitor Fer-1 administration could reverse the beneficial effects caused by Rg3 treatment while ferroptosis inducer Erastin treatment enhanced the effects...Rg3 inactivated the circFOXP1-miR-4477a-PD-L1 signaling axis to activate the immune function of CD8+ T cells, thereby inducing ferroptosis and apoptosis in GBC cells. This research recognizes the mechanism of Rg3-mediated anti-cancer effect and offers evidence for the potentiality of Rg3 in clinical application for GBC therapy.

Methylation increased PRMT4 DNA stability. Collectively, our data reveal that PRMT4 reduced erastin-induced ferroptosis in NPC cisplatin-resistant cells by Nrf2/GPX4 pathway, suggesting that targeting PRMT4 may present as a potential strategy against the development of NPC.

SLC7A9 promotes gastric cancer progression by acting as a suppressor of ferroptosis, independent of SLC7A11, which is negatively regulated by p53.

Finally, after erastin-induced ferroptosis, Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and other experiments were conducted to investigate whether the FOXM1/IDO1 axis regulates M2 macrophage polarization through ferroptosis...Lastly, FOXM1/IDO1 inhibited ferroptosis, promoting M2 macrophage polarization, thereby advancing TNBC progression. In conclusions, FOXM1 derived from TNBC cell-derived exosomes activated IDO1 transcription in TAMs to inhibit ferroptosis, promoting TAMs' M2 polarization and exerting carcinogenic effects.

Importantly, metformin reversed FFA-induced iron accumulation, and this effect was attenuated by ferrostatin-1 but enhanced by erastin, RSL3, and si-GPX4. In conclusion, our findings indicate that metformin may protect against MAFLD by inhibiting iron accumulation and Lp-PLA2 expression through the ROS, ferroptosis, and apoptosis signaling pathways. This study highlights potential therapeutic strategies for managing MAFLD-related risks and emphasizes the diverse roles of metformin in maintaining hepatocyte balance.

Collectively, these data indicate that HPV16 integration hot spot c-Myc plays a novel and indispensable role in ferroptosis resistance by regulating the miR-142-5p/HOXA5/SLC7A11 signalling axis and suggest a potential therapeutic approach for HPV16 integration-related CSCC.

Similar results were observed in hepatocarcinoma cells treated with erastin, an xCT inhibitor. These findings reveal an unappreciated role of cysteine in regulating the growth of malignant cancer cells and deepen our understanding of the cytotoxic effect of xCT inhibitor to prevent cancer cell proliferation.

Erastin was used to construct ferroptosis induction models...Mechanistically, csi-miR-96-5p and PTEN knockout significantly inhibited ferroptosis through a decrease in ferrous ion (Fe2+) and malondialdehyde (MDA), and an increase in glutathione reductase (GSH), Solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In conclusion, loss of PTEN promoted the progression of cholangiocarcinoma via the ferroptosis pathway and csi-miR-96-5p delivered by CS-EVs may mediate this process.

Using erastin to induce ferroptosis enhanced the efficacy of ALA-PDT on OLK cells by disrupting the antioxidant system and further elevating intracellular reactive oxygen species levels, leading to increased apoptosis. Furthermore, this combined modality also enhanced the efficacy of ALA-PDT on 4-nitroquinoline-1-oxide (4NQO)-induced OLK lesions in mice. In summary, ferroptosis induction may serve as a potential strategy to enhance the efficacy of ALA-PDT for OLK treatment.

In vivo, USP52 depletion combined with ferroptosis triggers imidazole ketone Erastin (IKE) synergistically restrains BLCA progression by inducing ferroptosis. These findings elucidate the role of the USP52-xCT axis in BLCA and highlight the therapeutic potential of targeting USP52 and ferroptosis inducers in BLCA.

It was observed that B16F10 and A375 melanoma cells with loss of CYGB expression were highly sensitive to ferroptosis inducers RSL3 and erastin, whereas G361 melanoma cells with highly enriched CYGB were resistant to RSL3 or erastin. In vivo study also demonstrated that CYGB overexpression rendered xenograft melanoma much more resist to RSL3 treatment. Based on these findings, CYGB is a potential therapeutic biomarker to screen the melanoma patients who are most likely benefit from ferroptosis treatment.

The prognosis for patients with DLBCL was worse when FASN was highly expressed, particularly in those undergoing chemotherapy for Adriamycin (ADM)...It is noteworthy that this effect was achieved by inhibiting ferroptosis, since Fer-1 (a ferroptosis inhibitor) treatment significantly recovered the effects of silencing FASN on inhibiting ferroptosis, while Erastin (a ferroptosis inducer) treatment attenuated the impact of overexpressing FASN. Mechanistically, FASN activated NF-κB/STAT3 signaling pathway through phosphorylating the upstream IKKα and IκBα, and the activated STAT3 promoted GPX4 expression by directly binding to GPX4 promoter. FASN inhibits ferroptosis in DLBCL via NF-κB/STAT3/GPX4 signaling pathway, indicating its critical role in mediating ADM resistance of DLBCL.

Our finding demonstrated for the first time, that imperatorin treatment holds therapeutic potential in a UUO mouse model of CKD and inhibits the erastin-induced oxidative stress, ferroptosis, and subsequent lipid peroxidation in vitro. This highlights the potential of imperatorin as a future therapeutic target for ferroptosis to improve the progression of CKD.

We used erastin-treated cells as a positive control and cells treated with HQ combined with deferoxamine mesylate (DFO) and ferrostain-1 (Fer-1)-treated cells as the negative controls. Notably, the activation of TFRC and the inhibition of FTH1 and System Xc- (cystine-glutamate reverse transporter protein) /GPX4 were associated with HQ-induced ferroptosis. These results provide novel insights into how HQ exacerbates haematopoietic cytotoxicity and provide potential targets for the prevention of HQ-induced diseases.

Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc-.

FAM230B knockdown favored ferroptosis and increased BTF3 expression, while its overexpression mitigated erastin-induced ferroptosis in GC cells. Additionally, BTF3 overexpression was found to negate miR-27a-5p's ferroptosis-promoting effects in GC cells. Collectively, our study demonstrates that the m6A modification of FAM230B by METTL3 plays a crucial role in promoting GC progression by reducing ferroptosis, through the modulation of the miR-27a-5p/BTF3 axis.

Chromatin immunoprecipitation and RNA immunoprecipitation analysis monitored the correlation among LINC01232, H3K27ac, p300 and ARNTL2. LINC01232 or ARNTL2 knockdown facilitated erastin-induced ferroptosis. The interaction between LINC01232 and p300 resulted in the enhancement of H3K27ac levels at ARNTL2 promoter to promote ARNTL2 transcriptional activity. ARNTL2 overexpression reversed the promoting effect of LINC01232 knockdown on ferroptosis. LINC01232 inhibited the ferroptosis in CRC by epigenetically upregulating the transcriptional activity of ARNTL2.

Conversely, BAP1-mediated suppression of disulfidptosis was largely abrogated when SLC7A11-mediated cystine uptake was inhibited by the knockout of SLC7A11 or erastin treatment...Consistent with these observations, the expression level of BAP1 was also positively correlated with NADPH-related genes in KIRC patients, though the underlying mechanism mediating NADPH regulation remains further investigation. In summary, our results revealed the role of BAP1 in the regulation disulfidptosis and provided new insights into the understanding of disulfidptosis in tumor development.

Hypoxia-induced BAP1 enhances erastin-induced ferroptosis in NPC by stabilizing H2A. Ferroptosis inducers targeting BAP1 may be an effective way to improve chemotherapy resistance in NPC, especially in the hypoxic microenvironment.