{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:23:56Z","timestamp":1773797036585,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["CU2018TEA457A103"],"award-info":[{"award-number":["CU2018TEA457A103"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["PN223LH010-035"],"award-info":[{"award-number":["PN223LH010-035"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["G.0C76.18N"],"award-info":[{"award-number":["G.0C76.18N"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["G.0B71.18N"],"award-info":[{"award-number":["G.0B71.18N"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["G.0B96.20N"],"award-info":[{"award-number":["G.0B96.20N"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["G.0A93.22N"],"award-info":[{"award-number":["G.0A93.22N"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["30826052"],"award-info":[{"award-number":["30826052"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["40007512"],"award-info":[{"award-number":["40007512"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF16\/MET_V\/007"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["20\/IBF\/039"],"award-info":[{"award-number":["20\/IBF\/039"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["F\/2016\/865"],"award-info":[{"award-number":["F\/2016\/865"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006338","name":"Vlaamse Interuniversitaire Raad (VLIR)-Belgium\/Ministerio de Educaci\u00f3n Superior (MES)","doi-asserted-by":"publisher","award":["F\/2020\/1505"],"award-info":[{"award-number":["F\/2020\/1505"]}],"id":[{"id":"10.13039\/501100006338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["CU2018TEA457A103"],"award-info":[{"award-number":["CU2018TEA457A103"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["PN223LH010-035"],"award-info":[{"award-number":["PN223LH010-035"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["G.0C76.18N"],"award-info":[{"award-number":["G.0C76.18N"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["G.0B71.18N"],"award-info":[{"award-number":["G.0B71.18N"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["G.0B96.20N"],"award-info":[{"award-number":["G.0B96.20N"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["G.0A93.22N"],"award-info":[{"award-number":["G.0A93.22N"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["30826052"],"award-info":[{"award-number":["30826052"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["40007512"],"award-info":[{"award-number":["40007512"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF16\/MET_V\/007"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["20\/IBF\/039"],"award-info":[{"award-number":["20\/IBF\/039"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["F\/2016\/865"],"award-info":[{"award-number":["F\/2016\/865"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008807","name":"Ministerio de Ciencia Tecnolog\u00eda y Medio Ambiente","doi-asserted-by":"publisher","award":["F\/2020\/1505"],"award-info":[{"award-number":["F\/2020\/1505"]}],"id":[{"id":"10.13039\/501100008807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FWO","award":["CU2018TEA457A103"],"award-info":[{"award-number":["CU2018TEA457A103"]}]},{"name":"FWO","award":["PN223LH010-035"],"award-info":[{"award-number":["PN223LH010-035"]}]},{"name":"FWO","award":["G.0C76.18N"],"award-info":[{"award-number":["G.0C76.18N"]}]},{"name":"FWO","award":["G.0B71.18N"],"award-info":[{"award-number":["G.0B71.18N"]}]},{"name":"FWO","award":["G.0B96.20N"],"award-info":[{"award-number":["G.0B96.20N"]}]},{"name":"FWO","award":["G.0A93.22N"],"award-info":[{"award-number":["G.0A93.22N"]}]},{"name":"FWO","award":["30826052"],"award-info":[{"award-number":["30826052"]}]},{"name":"FWO","award":["40007512"],"award-info":[{"award-number":["40007512"]}]},{"name":"FWO","award":["BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF16\/MET_V\/007"]}]},{"name":"FWO","award":["20\/IBF\/039"],"award-info":[{"award-number":["20\/IBF\/039"]}]},{"name":"FWO","award":["F\/2016\/865"],"award-info":[{"award-number":["F\/2016\/865"]}]},{"name":"FWO","award":["F\/2020\/1505"],"award-info":[{"award-number":["F\/2020\/1505"]}]},{"name":"Special Research Fund UGent","award":["CU2018TEA457A103"],"award-info":[{"award-number":["CU2018TEA457A103"]}]},{"name":"Special Research Fund UGent","award":["PN223LH010-035"],"award-info":[{"award-number":["PN223LH010-035"]}]},{"name":"Special Research Fund UGent","award":["G.0C76.18N"],"award-info":[{"award-number":["G.0C76.18N"]}]},{"name":"Special Research Fund UGent","award":["G.0B71.18N"],"award-info":[{"award-number":["G.0B71.18N"]}]},{"name":"Special Research Fund UGent","award":["G.0B96.20N"],"award-info":[{"award-number":["G.0B96.20N"]}]},{"name":"Special Research Fund UGent","award":["G.0A93.22N"],"award-info":[{"award-number":["G.0A93.22N"]}]},{"name":"Special Research Fund UGent","award":["30826052"],"award-info":[{"award-number":["30826052"]}]},{"name":"Special Research Fund UGent","award":["40007512"],"award-info":[{"award-number":["40007512"]}]},{"name":"Special Research Fund UGent","award":["BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF16\/MET_V\/007"]}]},{"name":"Special Research Fund UGent","award":["20\/IBF\/039"],"award-info":[{"award-number":["20\/IBF\/039"]}]},{"name":"Special Research Fund UGent","award":["F\/2016\/865"],"award-info":[{"award-number":["F\/2016\/865"]}]},{"name":"Special Research Fund UGent","award":["F\/2020\/1505"],"award-info":[{"award-number":["F\/2020\/1505"]}]},{"name":"Foundation against Cancer","award":["CU2018TEA457A103"],"award-info":[{"award-number":["CU2018TEA457A103"]}]},{"name":"Foundation against Cancer","award":["PN223LH010-035"],"award-info":[{"award-number":["PN223LH010-035"]}]},{"name":"Foundation against Cancer","award":["G.0C76.18N"],"award-info":[{"award-number":["G.0C76.18N"]}]},{"name":"Foundation against Cancer","award":["G.0B71.18N"],"award-info":[{"award-number":["G.0B71.18N"]}]},{"name":"Foundation against Cancer","award":["G.0B96.20N"],"award-info":[{"award-number":["G.0B96.20N"]}]},{"name":"Foundation against Cancer","award":["G.0A93.22N"],"award-info":[{"award-number":["G.0A93.22N"]}]},{"name":"Foundation against Cancer","award":["30826052"],"award-info":[{"award-number":["30826052"]}]},{"name":"Foundation against Cancer","award":["40007512"],"award-info":[{"award-number":["40007512"]}]},{"name":"Foundation against Cancer","award":["BOF16\/MET_V\/007"],"award-info":[{"award-number":["BOF16\/MET_V\/007"]}]},{"name":"Foundation against Cancer","award":["20\/IBF\/039"],"award-info":[{"award-number":["20\/IBF\/039"]}]},{"name":"Foundation against Cancer","award":["F\/2016\/865"],"award-info":[{"award-number":["F\/2016\/865"]}]},{"name":"Foundation against Cancer","award":["F\/2020\/1505"],"award-info":[{"award-number":["F\/2020\/1505"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ferroptosis is an iron-dependent cell death-driven by excessive peroxidation of polyunsaturated fatty acids (PUFAs) of membranes. A growing body of evidence suggests the induction of ferroptosis as a cutting-edge strategy in cancer treatment research. Despite the essential role of mitochondria in cellular metabolism, bioenergetics, and cell death, their function in ferroptosis is still poorly understood. Recently, mitochondria were elucidated as an important component in cysteine-deprivation-induced (CDI) ferroptosis, which provides novel targets in the search for new ferroptosis-inducing compounds (FINs). Here, we identified the natural mitochondrial uncoupler nemorosone as a ferroptosis inducer in cancer cells. Interestingly, nemorosone triggers ferroptosis by a double-edged mechanism. In addition to decreasing the glutathione (GSH) levels by blocking the System xc cystine\/glutamate antiporter (SLC7A11), nemorosone increases the intracellular labile Fe2+ pool via heme oxygenase-1 (HMOX1) induction. Interestingly, a structural variant of nemorosone (O-methylated nemorosone), having lost the capacity to uncouple mitochondrial respiration, does not trigger cell death anymore, suggesting that the mitochondrial bioenergetic disruption via mitochondrial uncoupling is necessary for nemorosone-induced ferroptosis. Our results open novel opportunities for cancer cell killing by mitochondrial uncoupling-induced ferroptosis.<\/jats:p>","DOI":"10.3390\/cells12050735","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T04:05:40Z","timestamp":1677470740000},"page":"735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Mechanisms of Nemorosone-Induced Ferroptosis in Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1588-9231","authenticated-orcid":false,"given":"Roberto","family":"Fern\u00e1ndez-Acosta","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Institute of Pharmacy and Food, University of Havana, 222 St. # 2317, La Coronela, La Lisa, Havana 13600, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Behrouz","family":"Hassannia","sequence":"additional","affiliation":[{"name":"Cell Death and Inflammation Unit, VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology (DBMB), Ghent University, 9052 Ghent, Belgium"},{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-2458","authenticated-orcid":false,"given":"Jurgen","family":"Caroen","sequence":"additional","affiliation":[{"name":"Laboratory for Organic and Bio-Organic Synthesis, Department of Organic and Macromolecular Chemistry, Ghent University, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bartosz","family":"Wiernicki","sequence":"additional","affiliation":[{"name":"Cell Death and Inflammation Unit, VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology (DBMB), Ghent University, 9052 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Alvarez-Alminaque","sequence":"additional","affiliation":[{"name":"Center for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, 222 St. # 2317, La Coronela, La Lisa, Havana 13600, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Verstraeten","sequence":"additional","affiliation":[{"name":"Cell Death and Inflammation Unit, VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology (DBMB), Ghent University, 9052 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Van der Eycken","sequence":"additional","affiliation":[{"name":"Laboratory for Organic and Bio-Organic Synthesis, Department of Organic and Macromolecular Chemistry, Ghent University, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vandenabeele","sequence":"additional","affiliation":[{"name":"Cell Death and Inflammation Unit, VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology (DBMB), Ghent University, 9052 Ghent, Belgium"},{"name":"Methusalem Program, Ghent University, 9052 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1633-0974","authenticated-orcid":false,"given":"Tom","family":"Vanden Berghe","sequence":"additional","affiliation":[{"name":"Cell Death and Inflammation Unit, VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology (DBMB), Ghent University, 9052 Ghent, Belgium"},{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7040-7031","authenticated-orcid":false,"given":"Gilberto L.","family":"Pardo-Andreu","sequence":"additional","affiliation":[{"name":"Center for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, 222 St. # 2317, La Coronela, La Lisa, Havana 13600, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6427","DOI":"10.1016\/0040-4039(96)00656-9","article-title":"Floral resins of Clusia spp.: Chemical composition and biological function","volume":"37","author":"Porto","year":"1996","journal-title":"Tetrahedron Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0031-9422(00)00510-0","article-title":"Nemorosone, the major constituent of floral resins of Clusia rosea","volume":"57","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1515\/znc-2002-3-429","article-title":"Polyisoprenylated benzophenones in Cuban propolis; biological activity of nemorosone","volume":"57","year":"2002","journal-title":"Z. Naturforsch."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1111\/j.1582-4934.2008.00232.x","article-title":"Cytotoxic activity of nemorosone in neuroblastoma cells","volume":"12","author":"Malak","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/j.1476-5381.2010.01125.x","article-title":"Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR)","volume":"162","author":"Holtrup","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.mito.2010.10.008","article-title":"The anti-cancer agent nemorosone is a new potent protonophoric mitochondrial uncoupler","volume":"11","author":"Tudella","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1139\/Y10-100","article-title":"Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells","volume":"89","author":"Popolo","year":"2011","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.phymed.2014.11.007","article-title":"Effects of nemorosone, isolated from the plant Clusia rosea, on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines","volume":"22","author":"Camargo","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cbi.2015.01.010","article-title":"The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling","volume":"228","author":"Reis","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104173","DOI":"10.1016\/j.fitote.2019.104173","article-title":"Chemosensitizing activity of Cuban propolis and nemorosone in doxorubicin resistant human colon carcinoma cells","volume":"136","author":"Gabbia","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fri\u00f3n-Herrera, Y., Gabbia, D., Scaffidi, M., Zagni, L., Cuesta-Rubio, O., Martin, S.D., and Carrara, M. (2020). The Cuban propolis component nemorosone inhibits proliferation and metastatic properties of human colorectal cancer cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051827"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1590\/S0102-695X2011005000148","article-title":"Assessment of estrogenic, mutagenic and antimutagenic activity of nemorosone","volume":"21","author":"Camargo","year":"2011","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Camargo, M., Prieto, A., Resende, F., Boldrin, P., Cardoso, C., Fern\u00e1ndez, M., Molina-Molina, J., Olea, N., Vilegas, W., and Cuesta-Rubio, O. (2013). Evaluation of estrogenic, antiestrogenic and genotoxic activity of nemorosone, the major compound found in brown cuban propolis. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-201"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"428","DOI":"10.5414\/CPP46428","article-title":"Nemorosone blocks proliferation and induces apoptosis in leukemia cells","volume":"46","author":"Malak","year":"2008","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_15","first-page":"6417","article-title":"Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors","volume":"34","author":"Lachaier","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4143\/crt.2016.572","article-title":"Ferroptosis: A novel anti-tumor action for cisplatin","volume":"50","author":"Guo","year":"2018","journal-title":"Cancer Res. Treat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1172\/JCI99032","article-title":"Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma","volume":"128","author":"Hassannia","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"774957","DOI":"10.3389\/fcell.2021.774957","article-title":"Emerging mechanisms and disease implications of ferroptosis: Potential applications of natural products","volume":"9","author":"Ge","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/s41419-020-03118-0","article-title":"Excessive phospholipid peroxidation distinguishes ferroptosis from other cell death modes including pyroptosis","volume":"11","author":"Wiernicki","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1089\/ars.2020.8175","article-title":"Ferroptosis: Biological rust of lipid membranes","volume":"35","author":"Hassannia","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.ccell.2019.04.002","article-title":"Targeting ferroptosis to iron out cancer","volume":"35","author":"Hassannia","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.molcel.2018.10.042","article-title":"Role of mitochondria in ferroptosis","volume":"73","author":"Gao","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101222","DOI":"10.1016\/j.molmet.2021.101222","article-title":"Exploring the therapeutic potential of mitochondrial uncouplers in cancer","volume":"51","author":"Shrestha","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8840","DOI":"10.1002\/anie.200703886","article-title":"Differentiation of nonconventional \u201ccarbanions\u201d-the total synthesis of nemorosone and clusianone","volume":"46","author":"Tsukano","year":"2007","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1021\/acs.orglett.5b01121","article-title":"Total synthesis of (-)-nemorosone and (+)-secohyperforin","volume":"17","author":"Sparling","year":"2015","journal-title":"Org. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101413","DOI":"10.1016\/j.redox.2019.101413","article-title":"AR ubiquitination induced by the curcumin analog suppresses growth of temozolomide-resistant glioblastoma through disrupting GPX4-mediated redox homeostasis","volume":"30","author":"Chena","year":"2020","journal-title":"Redox Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.2147\/OTT.S242567","article-title":"Bufalin induces glioma cell death by apoptosis or necroptosis","volume":"13","author":"LingHu","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/nprot.2016.085","article-title":"A real-time fluorometric method for the simultaneous detection of cell death type and rate","volume":"11","author":"Grootjans","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Acosta, R., Iriarte-Mesa, C., Alvarez-Alminaque, D., Hassannia, B., D\u00edaz-Garc\u00eda, A.M., Vandenabeele, P., Berghe, T.V., and Andreu, G.L.P. (2022). Novel iron oxide nanoparticles induce ferroptosis in a panel of cancer cell lines. Molecules, 27.","DOI":"10.3390\/molecules27133970"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dykens, J., and Will, Y. (2008). Drug-Induced Mitochondrial Dysfunction, John Wiley & Sons.","DOI":"10.1002\/9780470372531"},{"key":"ref_32","unstructured":"Andrews, S. (2022, June 14). A Quality Control Tool for High throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lawrence, M., Huber, W., Pag\u00e8s, H., Aboyoun, P., Carlson, M., Gentleman, R., Morgan, M.T., and Carey, V.J. (2013). Software for computing and annotating genomic ranges. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003118"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/S0891-5849(02)01360-6","article-title":"The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults","volume":"34","author":"Yant","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mam.2008.05.005","article-title":"Regulation of glutathione synthesis","volume":"30","author":"Lu","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E4966","DOI":"10.1073\/pnas.1603244113","article-title":"Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis","volume":"113","author":"Yang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e02523","DOI":"10.7554\/eLife.02523","article-title":"Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis","volume":"3","author":"Dixon","year":"2014","journal-title":"eLife"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrc3278","article-title":"NRF2 and cancer: The good, the bad and the importance of context","volume":"12","author":"Sporn","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.pharmtox.010909.105600","article-title":"Mechanisms of Cell Protection By Heme Oxygenase-1","volume":"50","author":"Gozzelino","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fphar.2012.00068","article-title":"Metalloporphyrins\u2014An update","volume":"3","author":"Schulz","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1016\/j.cell.2022.06.003","article-title":"Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications","volume":"185","author":"Stockwell","year":"2022","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41419-021-03998-w","article-title":"Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines","volume":"12","author":"Zheng","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.3174\/ajnr.A1242","article-title":"Analysis of 11C-methionine uptake in low-grade gliomas and correlation with proliferative activity","volume":"29","author":"Kato","year":"2008","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00726-011-0864-8","article-title":"The transsulfuration pathway: A source of cysteine for glutathione in astrocytes","volume":"42","author":"McBean","year":"2012","journal-title":"Amino Acids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.taap.2011.04.011","article-title":"The anti-cancer agent guttiferone-A permeabilizes mitochondrial membrane: Ensuing energetic and oxidative stress implications","volume":"253","author":"Tudella","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"77","DOI":"10.56499\/jppres19.561_7.2.77","article-title":"The mitochondrial uncoupling as a promising pharmacological target against cancer","volume":"7","year":"2019","journal-title":"J. Pharm. Pharmacogn. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.chembiol.2015.11.016","article-title":"Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity","volume":"23","author":"Shimada","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.7150\/ijbs.59404","article-title":"Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells","volume":"17","author":"Wei","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24393","DOI":"10.18632\/oncotarget.5162","article-title":"Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death","volume":"6","author":"Kwon","year":"2015","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"658315","DOI":"10.3389\/fimmu.2021.658315","article-title":"The diverse roles of heme oxygenase-1 in tumor progression","volume":"12","author":"Ngan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chiang, S.-K., Chen, S.-E., and Chang, L.-C. (2019). A dual role of heme oxygenase-1 in cancer cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010039"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"baw100","DOI":"10.1093\/database\/baw100","article-title":"The harmonizome: A collection of processed datasets gathered to serve and mine knowledge about genes and proteins","volume":"2016","author":"Rouillard","year":"2016","journal-title":"Database"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1165\/rcmb.2006-0340TR","article-title":"How many transcription factors does it take to turn on the heme oxygenase-1 gene?","volume":"36","author":"Alam","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1002\/cbic.200900721","article-title":"The identification of a novel natural activator of p300 histone acetyltranferase provides new insights into the modulation mechanism of this enzyme","volume":"11","author":"Piaz","year":"2010","journal-title":"ChemBioChem"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1128\/MCB.01639-08","article-title":"Acetylation of Nrf2 by p300\/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response","volume":"29","author":"Sun","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.bbrc.2020.02.006","article-title":"The acetyltransferase p300 regulates NRF2 stability and localization","volume":"524","author":"Ganner","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Friedmann","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.molcel.2015.06.011","article-title":"Glutaminolysis and transferrin regulate ferroptosis","volume":"59","author":"Gao","year":"2015","journal-title":"Mol. Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/5\/735\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:42:03Z","timestamp":1760121723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/5\/735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":63,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cells12050735"],"URL":"https:\/\/doi.org\/10.3390\/cells12050735","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]}}}