{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:52:13Z","timestamp":1778687533125,"version":"3.51.4"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:00:00Z","timestamp":1410825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Ursolic acid, a natural pentacyclic triterpenic acid, possesses anticancer potential and diverse biological effects, but its correlation with glioblastoma multiforme cells and different modes of cell death is unclear. We studied the cellular actions of human glioblastoma multiforme DBTRG\u201005MG cells after ursolic acid treatment and explored cell\u2010selective killing effect of necrotic death as a cell fate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Ursolic acid effectively reversed temozolomide resistance and reduced DBTRG\u201005MG cell viability. Surprisingly, ursolic acid failed to stimulate the apoptosis\u2010 and autophagy\u2010related signaling networks. The necrotic death was characterized by annexin V\/propidium iodide double\u2010positive detection and release of high\u2010mobility group protein B1 and lactate dehydrogenase. These ursolic acid elicited responses were accompanied by reactive oxygen species generation and glutathione depletion. Rapid mitochondrial dysfunction was paralleled by the preferential induction of necrosis, rather than apoptotic death. Mitochondrial permeability transition (MPT) is a phenomenon to provide the onset of mitochondrial depolarization during cellular necrosis. The opening of MPT pores that were mechanistically regulated by cyclophilin D, and adenosine triphosphate decline occurred in treated necrotic DBTRG\u201005MG cells. Cyclosporine A (an MPT pore inhibitor) prevented ursolic acid\u2010provoked necrotic death and the acid\u2010involved key regulators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study is the first to report that ursolic acid\u2010modified mitochondrial function triggers defective death by necrosis in DBTRG\u201005MG cells rather than augmenting programmed death.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201400051","type":"journal-article","created":{"date-parts":[[2014,8,16]],"date-time":"2014-08-16T10:09:46Z","timestamp":1408183786000},"page":"2146-2156","source":"Crossref","is-referenced-by-count":31,"title":["Ursolic acid triggers nonprogrammed death (necrosis) in human glioblastoma multiforme DBTRG\u201005MG cells through MPT pore opening and ATP decline"],"prefix":"10.1002","volume":"58","author":[{"given":"Chi\u2010Cheng","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Food Science and Biotechnology National Chung Hsing University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo\u2010Ru","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology National Chung Hsing University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Jyuan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology National Chung Hsing University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gow\u2010Chin","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology National Chung Hsing University  Taichung Taiwan"},{"name":"Agricultural Biotechnology Center National Chung Hsing University  Taichung 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