{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:30:37Z","timestamp":1774438237797,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program","award":["NRF-2020R1F1A1072032"],"award-info":[{"award-number":["NRF-2020R1F1A1072032"]}]},{"name":"Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program","award":["2020R1C1C1011146"],"award-info":[{"award-number":["2020R1C1C1011146"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)","award":["NRF-2020R1F1A1072032"],"award-info":[{"award-number":["NRF-2020R1F1A1072032"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)","award":["2020R1C1C1011146"],"award-info":[{"award-number":["2020R1C1C1011146"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)\/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.<\/jats:p>","DOI":"10.3390\/ijms24087057","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:57:08Z","timestamp":1681268228000},"page":"7057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition"],"prefix":"10.3390","volume":"24","author":[{"given":"Myung-Ji","family":"Kang","sequence":"first","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5291-3942","authenticated-orcid":false,"given":"Hyung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun","family":"Oh","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"},{"name":"Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Song","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"},{"name":"Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Huh","sequence":"additional","affiliation":[{"name":"Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yoon","family":"Park","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"},{"name":"Departments of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon","family":"Oh","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yhun","family":"Park","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doo-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunju","family":"Ro","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-4859","authenticated-orcid":false,"given":"Sung-Tae","family":"Hong","sequence":"additional","affiliation":[{"name":"Departments of Anatomy & Cell Biology, Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-5414","authenticated-orcid":false,"given":"Su","family":"Lee","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of 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