{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:41:24Z","timestamp":1789792884341,"version":"4.0.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Cancer Institute"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ferroptosis is a form of iron-dependent cell death of interest for the development of novel anti-cancer therapies. Ferroptosis research uses a process of elimination based on assumed ferroptosis-specific inducers and inhibitors; these molecules however have off-target effects and cannot provide a comprehensive picture of overlapping pathways. We investigated whether pyroptosis\u2014a form of inflammatory cell death\u2014is initiated in cancer cells following treatment with the ferroptosis inducer RSL3. We treated 6 cancer cell lines with RSL3 alone or in combination with inhibitors of ferroptosis (Ferrostatin-1), caspases (zVADfmk), necroptosis (Necrostatin-1), BID (BI-6C9), or STING (H-151). Biomarkers of pyroptosis and ferroptosis were assessed using our novel quantitative multiplex immunoassay. Increased secretion of pyroptosis-associated cytokines (IL-1\u03b1, IL-1\u03b2, IL-18), and gasdermin D and E (GSDMD\/E) cleavage with parallel loss of respective full-length proteins\u2014both hallmarks of pyroptosis\u2014were recorded in 5\/6 cell lines following RSL3 treatment. RSL3 cytotoxicity was blocked by Ferostatin-1; BID and STING inhibitors also prevented GSDMD\/E cleavage. We conclude that the ferroptosis-inducer RSL3 triggers pyroptosis in cancer cells; further work is required to elucidate the role of mitochondria in this process. Measurement of pathway-specific protein biomarkers is therefore necessary to identify the exact mechanism of action of novel cytotoxic agents.<\/jats:p>","DOI":"10.1038\/s41598-025-11368-1","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T13:49:43Z","timestamp":1752328183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Potent ferroptosis agent RSL3 induces cleavage of Pyroptosis-Specific gasdermins in Cancer cells"],"prefix":"10.1038","volume":"15","author":[{"given":"William G.","family":"Herrick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huong-Lan","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca R.","family":"Tomaino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Beall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeevan","family":"Govindharajulu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kuhlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph E.","family":"Parchment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Doroshow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva K.","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"11368_CR1","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"SJ Dixon","year":"2012","unstructured":"Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060\u20131072 (2012).","journal-title":"Cell"},{"key":"11368_CR2","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1016\/j.bbagen.2009.04.007","volume":"1790","author":"S Toppo","year":"2009","unstructured":"Toppo, S., Flohe, L., Ursini, F., Vanin, S. & Maiorino, M. Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme. Biochim. Biophys. Acta. 1790, 1486\u20131500 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"11368_CR3","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41392-020-00428-9","volume":"6","author":"HF Yan","year":"2021","unstructured":"Yan, H. F. et al. Ferroptosis: mechanisms and links with diseases. Signal. Transduct. Target. Ther. 6, 49 (2021).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"11368_CR4","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41586-019-1707-0","volume":"575","author":"S Doll","year":"2019","unstructured":"Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693\u2013698 (2019).","journal-title":"Nature"},{"key":"11368_CR5","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","volume":"25","author":"L Galluzzi","year":"2018","unstructured":"Galluzzi, L. et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell. Death Differ. 25, 486\u2013541 (2018).","journal-title":"Cell. Death Differ."},{"key":"11368_CR6","doi-asserted-by":"publisher","first-page":"637162","DOI":"10.3389\/fcell.2021.637162","volume":"9","author":"X Chen","year":"2021","unstructured":"Chen, X., Comish, P. B., Tang, D. & Kang, R. Characteristics and biomarkers of ferroptosis. Front. Cell. Dev. Biol. 9, 637162 (2021).","journal-title":"Front. Cell. Dev. Biol."},{"key":"11368_CR7","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nchembio.2238","volume":"13","author":"VE Kagan","year":"2017","unstructured":"Kagan, V. E. et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13, 81\u201390 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"11368_CR8","doi-asserted-by":"publisher","first-page":"3411","DOI":"10.1016\/j.celrep.2020.02.049","volume":"30","author":"H Feng","year":"2020","unstructured":"Feng, H. et al. Transferrin receptor is a specific ferroptosis marker. Cell. Rep. 30, 3411\u20133423e3417 (2020).","journal-title":"Cell. Rep."},{"key":"11368_CR9","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","volume":"156","author":"WS Yang","year":"2014","unstructured":"Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317\u2013331 (2014).","journal-title":"Cell"},{"key":"11368_CR10","doi-asserted-by":"publisher","first-page":"e02523","DOI":"10.7554\/eLife.02523","volume":"3","author":"SJ Dixon","year":"2014","unstructured":"Dixon, S. J. et al. Pharmacological Inhibition of cystine-glutamate exchange induces Endoplasmic reticulum stress and ferroptosis. Elife 3, e02523 (2014).","journal-title":"Elife"},{"key":"11368_CR11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.freeradbiomed.2021.05.023","volume":"171","author":"D Soriano-Castell","year":"2021","unstructured":"Soriano-Castell, D., Currais, A. & Maher, P. Defining a Pharmacological inhibitor fingerprint for oxytosis\/ferroptosis. Free Radic Biol. Med. 171, 219\u2013231 (2021).","journal-title":"Free Radic Biol. Med."},{"key":"11368_CR12","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","volume":"22","author":"X Jiang","year":"2021","unstructured":"Jiang, X., Stockwell, B. R. & Conrad, M. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell. Biol. 22, 266\u2013282 (2021).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"11368_CR13","doi-asserted-by":"crossref","unstructured":"Yuk, H., Abdullah, M., Kim, D. H., Lee, H. & Lee, S. J. Necrostatin-1 prevents ferroptosis in a RIPK1- and IDO-Independent manner in hepatocellular carcinoma. Antioxidants (Basel) 10, 1347 (2021).","DOI":"10.3390\/antiox10091347"},{"key":"11368_CR14","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/sj.cdd.4402044","volume":"14","author":"D Chauvier","year":"2007","unstructured":"Chauvier, D., Ankri, S., Charriaut-Marlangue, C., Casimir, R. & Jacotot, E. Broad-spectrum caspase inhibitors: from myth to reality? Cell. Death Differ. 14, 387\u2013391 (2007).","journal-title":"Cell. Death Differ."},{"key":"11368_CR15","first-page":"6417","volume":"34","author":"E Lachaier","year":"2014","unstructured":"Lachaier, E. et al. Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors. Anticancer Res. 34, 6417\u20136422 (2014).","journal-title":"Anticancer Res."},{"key":"11368_CR16","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41419-021-03998-w","volume":"12","author":"J Zheng","year":"2021","unstructured":"Zheng, J. et al. Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines. Cell. Death Dis. 12, 698 (2021).","journal-title":"Cell. Death Dis."},{"key":"11368_CR17","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13046-021-01959-x","volume":"40","author":"Y Tan","year":"2021","unstructured":"Tan, Y. et al. Pyroptosis: a new paradigm of cell death for fighting against cancer. J. Exp. Clin. Cancer Res. 40, 153 (2021).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"11368_CR18","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nature18629","volume":"535","author":"X Liu","year":"2016","unstructured":"Liu, X. et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535, 153\u2013158 (2016).","journal-title":"Nature"},{"key":"11368_CR19","doi-asserted-by":"publisher","first-page":"7858","DOI":"10.1073\/pnas.1607769113","volume":"113","author":"RA Aglietti","year":"2016","unstructured":"Aglietti, R. A. et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc. Natl. Acad. Sci. U S A. 113, 7858\u20137863 (2016).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"11368_CR20","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/cr.2016.100","volume":"26","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell. Res. 26, 1007\u20131020 (2016).","journal-title":"Cell. Res."},{"key":"11368_CR21","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41392-021-00507-5","volume":"6","author":"P Yu","year":"2021","unstructured":"Yu, P. et al. Pyroptosis: mechanisms and diseases. Signal. Transduct. Target. Ther. 6, 128 (2021).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"11368_CR22","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3389\/fcimb.2019.00406","volume":"9","author":"RKS Malireddi","year":"2019","unstructured":"Malireddi, R. K. S., Kesavardhana, S. & Kanneganti, T. D. ZBP1 and TAK1: master regulators of NLRP3 inflammasome\/pyroptosis, apoptosis, and necroptosis (PAN-optosis). Front. Cell. Infect. Microbiol. 9, 406 (2019).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"11368_CR23","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/s41580-020-0270-8","volume":"21","author":"S Bedoui","year":"2020","unstructured":"Bedoui, S., Herold, M. J. & Strasser, A. Emerging connectivity of programmed cell death pathways and its physiological implications. Nat. Rev. Mol. Cell. Biol. 21, 678\u2013695 (2020).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"11368_CR24","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/s41586-019-1770-6","volume":"575","author":"M Fritsch","year":"2019","unstructured":"Fritsch, M. et al. Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature 575, 683\u2013687 (2019).","journal-title":"Nature"},{"key":"11368_CR25","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/s41556-020-0565-1","volume":"22","author":"M Riegman","year":"2020","unstructured":"Riegman, M. et al. Ferroptosis occurs through an osmotic mechanism and propagates independently of cell rupture. Nat. Cell. Biol. 22, 1042\u20131048 (2020).","journal-title":"Nat. Cell. Biol."},{"key":"11368_CR26","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.15252\/embj.201694696","volume":"35","author":"L Sborgi","year":"2016","unstructured":"Sborgi, L. et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 35, 1766\u20131778 (2016).","journal-title":"EMBO J."},{"key":"11368_CR27","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1080\/15548627.2020.1739447","volume":"17","author":"C Li","year":"2021","unstructured":"Li, C. et al. Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. Autophagy 17, 948\u2013960 (2021).","journal-title":"Autophagy"},{"key":"11368_CR28","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2017.09.039","volume":"171","author":"MM Gaidt","year":"2017","unstructured":"Gaidt, M. M. et al. The DNA inflammasome in human myeloid cells is initiated by a STING-Cell death program upstream of NLRP3. Cell 171, 1110\u20131124e1118 (2017).","journal-title":"Cell"},{"key":"11368_CR29","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.redox.2017.03.007","volume":"12","author":"S Neitemeier","year":"2017","unstructured":"Neitemeier, S. et al. BID links ferroptosis to mitochondrial cell death pathways. Redox Biol. 12, 558\u2013570 (2017).","journal-title":"Redox Biol."},{"key":"11368_CR30","doi-asserted-by":"publisher","first-page":"e21757","DOI":"10.1096\/fj.202100085R","volume":"35","author":"C de Torre-Minguela","year":"2021","unstructured":"de Torre-Minguela, C., Gomez, A. I., Couillin, I. & Pelegrin, P. Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis. FASEB J. 35, e21757 (2021).","journal-title":"FASEB J."},{"key":"11368_CR31","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1038\/s41422-018-0090-y","volume":"28","author":"B Zhou","year":"2018","unstructured":"Zhou, B. et al. Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis. Cell. Res. 28, 1171\u20131185 (2018).","journal-title":"Cell. Res."},{"key":"11368_CR32","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tcb.2015.10.014","volume":"26","author":"WS Yang","year":"2016","unstructured":"Yang, W. S. & Stockwell, B. R. Ferroptosis: death by lipid peroxidation. Trends Cell. Biol. 26, 165\u2013176 (2016).","journal-title":"Trends Cell. Biol."},{"key":"11368_CR33","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.chom.2018.05.009","volume":"24","author":"R Kang","year":"2018","unstructured":"Kang, R. et al. Lipid peroxidation drives gasdermin D-Mediated pyroptosis in lethal polymicrobial Sepsis. Cell. Host Microbe. 24, 97\u2013108e104 (2018).","journal-title":"Cell. Host Microbe"},{"key":"11368_CR34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.freeradbiomed.2021.07.009","volume":"173","author":"R Fan","year":"2021","unstructured":"Fan, R., Sui, J., Dong, X., Jing, B. & Gao, Z. Wedelolactone alleviates acute pancreatitis and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis. Free Radic Biol. Med. 173, 29\u201340 (2021).","journal-title":"Free Radic Biol. Med."},{"key":"11368_CR35","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.3389\/fimmu.2019.01904","volume":"10","author":"R Chen","year":"2019","unstructured":"Chen, R. et al. AGER-Mediated lipid peroxidation drives Caspase-11 inflammasome activation in Sepsis. Front. Immunol. 10, 1904 (2019).","journal-title":"Front. Immunol."},{"key":"11368_CR36","doi-asserted-by":"crossref","unstructured":"Tang, L. et al. Induction mechanism of ferroptosis, necroptosis, and pyroptosis: A novel therapeutic target in nervous system diseases. Int J. Mol. Sci 24, 10127 (2023).","DOI":"10.3390\/ijms241210127"},{"key":"11368_CR37","doi-asserted-by":"publisher","first-page":"109235","DOI":"10.1016\/j.celrep.2021.109235","volume":"35","author":"C Xu","year":"2021","unstructured":"Xu, C. et al. The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity. Cell. Rep. 35, 109235 (2021).","journal-title":"Cell. Rep."},{"key":"11368_CR38","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.brainres.2018.10.023","volume":"1706","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y. et al. Ferroptosis inhibitor SRS 16\u201386 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury. Brain Res. 1706, 48\u201357 (2019).","journal-title":"Brain Res."},{"key":"11368_CR39","unstructured":"Herrick, W. G., Govindharajulu, J., Parchment, R. E., Doroshow, J. H. & Srivastava, A. K. in AACR Annual Meeting 2023. (American Association for Cancer Research)."},{"key":"11368_CR40","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nchembio.2229","volume":"13","author":"MC Okondo","year":"2017","unstructured":"Okondo, M. C. et al. DPP8 and DPP9 Inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat. Chem. Biol. 13, 46\u201353 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"11368_CR41","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1158\/1078-0432.CCR-14-3156","volume":"22","author":"AK Srivastava","year":"2016","unstructured":"Srivastava, A. K. et al. Effect of a Smac mimetic (TL32711, Birinapant) on the apoptotic program and apoptosis biomarkers examined with validated multiplex immunoassays fit for clinical use. Clin. Cancer Res. 22, 1000\u20131010 (2016).","journal-title":"Clin. Cancer Res."},{"key":"11368_CR42","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.freeradbiomed.2018.01.019","volume":"117","author":"A Jelinek","year":"2018","unstructured":"Jelinek, A. et al. Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radic Biol. Med. 117, 45\u201357 (2018).","journal-title":"Free Radic Biol. Med."},{"key":"11368_CR43","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1016\/j.bbrc.2020.10.035","volume":"533","author":"F Kuang","year":"2020","unstructured":"Kuang, F., Liu, J., Li, C., Kang, R. & Tang, D. Cathepsin B is a mediator of organelle-specific initiation of ferroptosis. Biochem. Biophys. Res. Commun. 533, 1464\u20131469 (2020).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"11368_CR44","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s12276-022-00729-9","volume":"54","author":"W Zhang","year":"2022","unstructured":"Zhang, W. et al. Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis. Exp. Mol. Med. 54, 129\u2013142 (2022).","journal-title":"Exp. Mol. Med."},{"key":"11368_CR45","doi-asserted-by":"publisher","first-page":"15514","DOI":"10.1073\/pnas.1414859111","volume":"111","author":"J Yu","year":"2014","unstructured":"Yu, J. et al. Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy. Proc. Natl. Acad. Sci. U S A. 111, 15514\u201315519 (2014).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"11368_CR46","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/cdd.2010.92","volume":"18","author":"S Tobaben","year":"2011","unstructured":"Tobaben, S. et al. Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons. Cell. Death Differ. 18, 282\u2013292 (2011).","journal-title":"Cell. Death Differ."},{"key":"11368_CR47","doi-asserted-by":"publisher","first-page":"108887","DOI":"10.1016\/j.celrep.2021.108887","volume":"34","author":"K Tsuchiya","year":"2021","unstructured":"Tsuchiya, K. et al. Gasdermin D mediates the maturation and release of IL-1alpha downstream of inflammasomes. Cell. Rep. 34, 108887 (2021).","journal-title":"Cell. Rep."},{"key":"11368_CR48","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nature23007","volume":"547","author":"VS Viswanathan","year":"2017","unstructured":"Viswanathan, V. S. et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547, 453\u2013457 (2017).","journal-title":"Nature"},{"key":"11368_CR49","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.4049\/jimmunol.141.8.2629","volume":"141","author":"SM Laster","year":"1988","unstructured":"Laster, S. M., Wood, J. G. & Gooding, L. R. Tumor necrosis factor can induce both apoptic and necrotic forms of cell Lysis. J. Immunol. 141, 2629\u20132634 (1988).","journal-title":"J. Immunol."},{"key":"11368_CR50","doi-asserted-by":"publisher","first-page":"5155","DOI":"10.1038\/s41598-018-23408-0","volume":"8","author":"E Agmon","year":"2018","unstructured":"Agmon, E., Solon, J., Bassereau, P. & Stockwell, B. R. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci. Rep. 8, 5155 (2018).","journal-title":"Sci. Rep."},{"key":"11368_CR51","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1038\/s41418-020-00691-x","volume":"28","author":"L Pedrera","year":"2021","unstructured":"Pedrera, L. et al. Ferroptotic pores induce Ca(2+) fluxes and ESCRT-III activation to modulate cell death kinetics. Cell. Death Differ. 28, 1644\u20131657 (2021).","journal-title":"Cell. Death Differ."},{"key":"11368_CR52","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1111\/j.1462-5822.2006.00751.x","volume":"8","author":"SL Fink","year":"2006","unstructured":"Fink, S. L. & Cookson, B. T. Caspase-1-dependent pore formation during pyroptosis leads to osmotic Lysis of infected host macrophages. Cell. Microbiol. 8, 1812\u20131825 (2006).","journal-title":"Cell. Microbiol."},{"key":"11368_CR53","doi-asserted-by":"publisher","first-page":"102758","DOI":"10.1016\/j.redox.2023.102758","volume":"63","author":"AA Amoscato","year":"2023","unstructured":"Amoscato, A. A. et al. Formation of protein adducts with Hydroperoxy-PE electrophilic cleavage products during ferroptosis. Redox Biol. 63, 102758 (2023).","journal-title":"Redox Biol."},{"key":"11368_CR54","doi-asserted-by":"publisher","first-page":"e1054549","DOI":"10.1080\/23723556.2015.1054549","volume":"2","author":"Y Yu","year":"2015","unstructured":"Yu, Y. et al. The ferroptosis inducer Erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol. Cell. Oncol. 2, e1054549 (2015).","journal-title":"Mol. Cell. Oncol."},{"key":"11368_CR55","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41586-020-2071-9","volume":"579","author":"Z Zhang","year":"2020","unstructured":"Zhang, Z. et al. Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature 579, 415\u2013420 (2020).","journal-title":"Nature"},{"key":"11368_CR56","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1038\/s41467-020-16043-9","volume":"11","author":"M Karmakar","year":"2020","unstructured":"Karmakar, M. et al. N-GSDMD trafficking to neutrophil organelles facilitates IL-1beta release independently of plasma membrane pores and pyroptosis. Nat. Commun. 11, 2212 (2020).","journal-title":"Nat. Commun."},{"key":"11368_CR57","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.1016\/j.celrep.2019.05.065","volume":"27","author":"SS Burgener","year":"2019","unstructured":"Burgener, S. S. et al. Cathepsin G Inhibition by Serpinb1 and Serpinb6 prevents programmed necrosis in neutrophils and monocytes and reduces GSDMD-Driven inflammation. Cell. Rep. 27, 3646\u20133656 (2019). e3645.","journal-title":"Cell. Rep."},{"key":"11368_CR58","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.taap.2008.07.008","volume":"232","author":"LM Elphick","year":"2008","unstructured":"Elphick, L. M. et al. Opposing roles for caspase and Calpain death proteases in L-glutamate-induced oxidative neurotoxicity. Toxicol. Appl. Pharmacol. 232, 258\u2013267 (2008).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"11368_CR59","doi-asserted-by":"crossref","unstructured":"De Backer, J. et al. Cytoglobin Silencing promotes melanoma malignancy but sensitizes for ferroptosis and pyroptosis therapy response. Antioxidants (Basel) 11, 1548 (2022).","DOI":"10.3390\/antiox11081548"},{"key":"11368_CR60","doi-asserted-by":"publisher","first-page":"112008","DOI":"10.1016\/j.celrep.2023.112008","volume":"42","author":"P Devant","year":"2023","unstructured":"Devant, P. et al. Gasdermin D pore-forming activity is redox-sensitive. Cell. Rep. 42, 112008 (2023).","journal-title":"Cell. Rep."},{"key":"11368_CR61","doi-asserted-by":"publisher","first-page":"114237","DOI":"10.1016\/j.celrep.2024.114237","volume":"43","author":"Y Tang","year":"2024","unstructured":"Tang, Y. et al. Cardiolipin oxidized by ROS from complex II acts as a target of gasdermin D to drive mitochondrial pore and heart dysfunction in endotoxemia. Cell. Rep. 43, 114237 (2024).","journal-title":"Cell. Rep."},{"key":"11368_CR62","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s12974-022-02602-y","volume":"19","author":"X Hu","year":"2022","unstructured":"Hu, X. et al. Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis. J. Neuroinflammation. 19, 242 (2022).","journal-title":"J. Neuroinflammation"},{"key":"11368_CR63","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/s41590-020-0699-0","volume":"21","author":"M Jia","year":"2020","unstructured":"Jia, M. et al. Redox homeostasis maintained by GPX4 facilitates STING activation. Nat. Immunol. 21, 727\u2013735 (2020).","journal-title":"Nat. Immunol."},{"key":"11368_CR64","doi-asserted-by":"publisher","first-page":"5061","DOI":"10.1073\/pnas.1818598116","volume":"116","author":"MA Davis","year":"2019","unstructured":"Davis, M. A. et al. Calpain drives pyroptotic vimentin cleavage, intermediate filament loss, and cell rupture that mediates immunostimulation. Proc. Natl. Acad. Sci. U S A. 116, 5061\u20135070 (2019).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"11368_CR65","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.arr.2016.05.008","volume":"32","author":"T Yamashima","year":"2016","unstructured":"Yamashima, T. Can \u2018calpain-cathepsin hypothesis\u2019 explain alzheimer neuronal death? Ageing Res. Rev. 32, 169\u2013179 (2016).","journal-title":"Ageing Res. Rev."},{"key":"11368_CR66","doi-asserted-by":"publisher","first-page":"118928","DOI":"10.1016\/j.bbamcr.2020.118928","volume":"1868","author":"P Nagakannan","year":"2021","unstructured":"Nagakannan, P., Islam, M. I., Conrad, M. & Eftekharpour, E. Cathepsin B is an executioner of ferroptosis. Biochim. Biophys. Acta Mol. Cell. Res. 1868, 118928 (2021).","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"11368_CR67","doi-asserted-by":"crossref","unstructured":"Bai, H. et al. GPX4 Inhibition contributes to NLRP3-Mediated pyroptosis and cognitive impairment in Ketamine-Exposed neonatal rats. Mol Neurobiol (2025).","DOI":"10.1007\/s12035-025-05042-w"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11368-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11368-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11368-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T08:11:51Z","timestamp":1757232711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11368-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,12]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["11368"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-11368-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,12]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no potential conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"25249"}}