{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:01:03Z","timestamp":1791234063401,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"3-4","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 81904085"],"award-info":[{"award-number":["No. 81904085"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Science and Technology Department of Jiangsu Province","award":["BK20191412"],"award-info":[{"award-number":["BK20191412"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Apoptosis"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute promyelocytic leukemia (APL) is a blood system disease caused by the accumulation of a large number of immature blood cells in bone marrow. Although the introduction of all-<jats:italic>trans<\/jats:italic> retinoic acid (ATRA) and arsenic has reached a high level of complete remission rate and 5-year disease-free survival rate, the occurrence of various adverse reactions still severely affects the quality of life of patients. As a natural product, honokiol (HNK) has the advantages of low toxicity and high efficiency, and it is a potential drug for the treatment of cancer. Since cancer cells can escape apoptotic cell death through multiple adaptive mechanisms, HNK, a drug that induces cancer cell death in a nonapoptotic way, has attracted much interest. We found that HNK reduced the viability of human APL cell line (NB4 cells) by inducing paraptosis-like cell death. The process was accompanied by excessive reactive oxygen species (ROS), mitochondrial damage, endoplasmic reticulum stress, and increased microtubule-associated protein 1 light chain 3 (LC3) processing. The inactivation of proteasome activity was the main cause of misfolded and unfolded protein accumulation in endoplasmic reticulum, such as LC3II\/I and p62. This phenomenon could be alleviated by adding cycloheximide (CHX), a protein synthesis inhibitor. We found that mTOR signaling pathway participated in paraptosis-like cell death induced by HNK in an autophagy-independent process. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway induced paraptosis of NB4 cells by promoting endoplasmic reticulum stress. In summary, these findings indicate that paraptosis may be a new way to treat APL, and provide novel insights into the potential mechanism of paraptosis-like cell death.<\/jats:p>","DOI":"10.1007\/s10495-020-01655-9","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T03:31:18Z","timestamp":1612841478000},"page":"195-208","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR &amp; MAPK signaling pathways activation"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-8511","authenticated-orcid":false,"given":"Xiaoli","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-2816","authenticated-orcid":false,"given":"Yaoyao","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9825-3097","authenticated-orcid":false,"given":"Danhong","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2058-9049","authenticated-orcid":false,"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-0392","authenticated-orcid":false,"given":"Ye","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7776-3653","authenticated-orcid":false,"given":"Zhaofeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-1101","authenticated-orcid":false,"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"1655_CR1","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1084\/jem.20131121","volume":"210","author":"GA Dos Santos","year":"2013","unstructured":"Dos Santos GA, Kats L, Pandolfi PP (2013) Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia. J Exp Med 210:2793\u20132802. https:\/\/doi.org\/10.1084\/jem.20131121","journal-title":"J Exp Med"},{"key":"1655_CR2","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/978-3-540-34594-7_7","volume":"313","author":"P Fenaux","year":"2007","unstructured":"Fenaux P, Wang ZZ, Degos L (2007) Treatment of acute promyelocytic leukemia by retinoids. Curr Top Microbiol Immunol 313:101\u2013128. https:\/\/doi.org\/10.1007\/978-3-540-34594-7_7","journal-title":"Curr Top Microbiol Immunol"},{"key":"1655_CR3","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s12185-013-1354-4","volume":"97","author":"A Tomita","year":"2013","unstructured":"Tomita A, Kiyoi H, Naoe T (2013) Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia. Int J Hematol 97:717\u2013725. https:\/\/doi.org\/10.1007\/s12185-013-1354-4","journal-title":"Int J Hematol"},{"issue":"15","key":"1655_CR4","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1182\/blood-2019-01-894980","volume":"133","author":"MA Sanz","year":"2019","unstructured":"Sanz MA, Fenaux P, Tallman MS, Estey EH, L\u00f6wenberg B, Naoe T, Lengfelder E, D\u00f6hner H, Burnett AK, Chen SJ, Mathews V, Iland H, Rego E, Kantarjian H, Ad\u00e8s L, Avvisati G, Montesinos P, Platzbecker U, Ravandi F, Russell NH, Lo-Coco F (2019) Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood 133(15):1630\u20131643. https:\/\/doi.org\/10.1182\/blood-2019-01-894980","journal-title":"Blood"},{"key":"1655_CR5","doi-asserted-by":"publisher","first-page":"14376","DOI":"10.1073\/pnas.97.26.14376","volume":"97","author":"S Sperandio","year":"2000","unstructured":"Sperandio S, de Belle I, Bredesen DE (2000) An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci USA 97:14376\u201314381. https:\/\/doi.org\/10.1073\/pnas.97.26.14376","journal-title":"Proc Natl Acad Sci USA"},{"key":"1655_CR6","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1002\/ijc.24064","volume":"124","author":"S Fulda","year":"2009","unstructured":"Fulda S (2009) Tumor resistance to apoptosis. Int J Cancer 124:511\u2013515. https:\/\/doi.org\/10.1002\/ijc.24064","journal-title":"Int J Cancer"},{"key":"1655_CR7","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.canlet.2008.05.008","volume":"270","author":"TS Chen","year":"2008","unstructured":"Chen TS, Wang XP, Sun L, Wang LX, Xing D, Mok M (2008) Taxol induces caspase-independent cytoplasmic vacuolization and cell death through endoplasmic reticulum (ER) swelling in ASTC-a-1 cells. Cancer Lett 270:164\u2013172. https:\/\/doi.org\/10.1016\/j.canlet.2008.05.008","journal-title":"Cancer Lett"},{"key":"1655_CR8","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1242\/jcs.00994","volume":"117","author":"Y Wang","year":"2004","unstructured":"Wang Y, Li X, Wang L, Ding P, Zhang Y, Han W, Ma D (2004) An alternative form of paraptosis-like cell death, triggered by TAJ\/TROY and enhanced by PDCD5 overexpression. J Cell Sci 117:1525\u20131532. https:\/\/doi.org\/10.1242\/jcs.00994","journal-title":"J Cell Sci"},{"key":"1655_CR9","doi-asserted-by":"publisher","first-page":"101061","DOI":"10.1016\/j.redox.2018.11.019","volume":"21","author":"X Chen","year":"2019","unstructured":"Chen X, Chen X, Zhang X, Wang L, Cao P, Rajamanickam V, Wu C, Zhou H, Cai Y, Liang G, Wang Y (2019) Curcuminoid B63 induces ROS-mediated paraptosis-like cell death by targeting TrxR1 in gastric cells. Redox Biol 21:101061. https:\/\/doi.org\/10.1016\/j.redox.2018.11.019","journal-title":"Redox Biol"},{"key":"1655_CR10","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cbi.2018.02.003","volume":"283","author":"J Xue","year":"2018","unstructured":"Xue J, Li R, Zhao X, Ma C, Lv X, Liu L, Liu P (2018) Morusin induces paraptosis-like cell death through mitochondrial calcium overload and dysfunction in epithelial ovarian cancer. Chem Biol Interact 283:59\u201374. https:\/\/doi.org\/10.1016\/j.cbi.2018.02.003","journal-title":"Chem Biol Interact"},{"key":"1655_CR11","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.pharmthera.2011.01.010","volume":"130","author":"YJ Lee","year":"2011","unstructured":"Lee YJ, Lee YM, Lee CK, Jung JK, Han SB, Hong JT (2011) Therapeutic applications of compounds in the Magnolia family. Pharmacol Ther 130:157\u2013176. https:\/\/doi.org\/10.1016\/j.pharmthera.2011.01.010","journal-title":"Pharmacol Ther"},{"key":"1655_CR12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3390\/cancers12010048","volume":"12","author":"CP Ong","year":"2019","unstructured":"Ong CP, Lee WL, Tang YQ, Yap WH (2019) Honokiol: A Review of Its Anticancer Potential and Mechanisms. Cancers (Basel) 12:48. https:\/\/doi.org\/10.3390\/cancers12010048","journal-title":"Cancers (Basel)"},{"key":"1655_CR13","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.bbrc.2012.12.063","volume":"430","author":"Y Wang","year":"2013","unstructured":"Wang Y, Zhu X, Yang Z, Zhao X (2013) Honokiol induces caspase-independent paraptosis via reactive oxygen species production that is accompanied by apoptosis in leukemia cells. Biochem Biophys Res Commun 430:876\u2013882. https:\/\/doi.org\/10.1016\/j.bbrc.2012.12.063","journal-title":"Biochem Biophys Res Commun"},{"key":"1655_CR14","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.2174\/156652412803833508","volume":"12","author":"S Arora","year":"2012","unstructured":"Arora S, Singh S, Piazza GA, Contreras CM, Panyam J, Singh AP (2012) Honokiol: a novel natural agent for cancer prevention and therapy. Curr Mol Med 12:1244\u20131252. https:\/\/doi.org\/10.2174\/156652412803833508","journal-title":"Curr Mol Med"},{"key":"1655_CR15","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s10815-018-1353-8","volume":"36","author":"M Fransolet","year":"2019","unstructured":"Fransolet M, No\u00ebl L, Henry L, Labied S, Blacher S, Nisolle M, Munaut C (2019) Evaluation of Z-VAD-FMK as an anti-apoptotic drug to prevent granulosa cell apoptosis and follicular death after human ovarian tissue transplantation. J Assist Reprod Genet 36:349\u2013359. https:\/\/doi.org\/10.1007\/s10815-018-1353-8","journal-title":"J Assist Reprod Genet"},{"key":"1655_CR16","doi-asserted-by":"publisher","first-page":"30993","DOI":"10.1074\/jbc.M303763200","volume":"27","author":"R Ilangovan","year":"2003","unstructured":"Ilangovan R, Marshall WL, Hua Y, Zhou J (2003) Inhibition of apoptosis by Z-VAD-fmk in SMN-depleted S2 cells. J Biol Chem 27:30993\u201330999. https:\/\/doi.org\/10.1074\/jbc.M303763200","journal-title":"J Biol Chem"},{"key":"1655_CR17","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.pharmthera.2016.01.003","volume":"162","author":"D Lee","year":"2016","unstructured":"Lee D, Kim IY, Saha S, Choi KS (2016) Paraptosis in the anti-cancer arsenal of natural products. Pharmacol Ther 162:120\u2013133. https:\/\/doi.org\/10.1016\/j.pharmthera.2016.01.003","journal-title":"Pharmacol Ther"},{"key":"1655_CR18","doi-asserted-by":"publisher","first-page":"e561","DOI":"10.1038\/cddis.2013.85","volume":"4","author":"M Bury","year":"2013","unstructured":"Bury M, Girault A, M\u00e9galizzi V, Spiegl-Kreinecker S, Mathieu V, Berger W, Evidente A, Kornienko A, Gailly P, Vandier C, Kiss R (2013) Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity. Cell Death Dis 4:e561. https:\/\/doi.org\/10.1038\/cddis.2013.85","journal-title":"Cell Death Dis"},{"key":"1655_CR19","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.1002\/jcp.22956","volume":"227","author":"WB Wang","year":"2012","unstructured":"Wang WB, Feng LX, Yue QX, Wu WY, Guan SH, Jiang BH, Yang M, Liu X, Guo DA (2012) Paraptosis accompanied by autophagy and apoptosis was induced by celastrol, a natural compound with influence on proteasome, ER stress and Hsp90. J Cell Physiol 227:2196\u20132206. https:\/\/doi.org\/10.1002\/jcp.22956","journal-title":"J Cell Physiol"},{"key":"1655_CR20","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1038\/onc.2009.118","volume":"28","author":"R Kar","year":"2009","unstructured":"Kar R, Singha PK, Venkatachalam MA, Saikumar P (2009) A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells. Oncogene 28:2556\u20132568. https:\/\/doi.org\/10.1038\/onc.2009.118","journal-title":"Oncogene"},{"key":"1655_CR21","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1002\/cncr.31335","volume":"124","author":"AV Onorati","year":"2018","unstructured":"Onorati AV, Dyczynski M, Ojha R, Amaravadi RK (2018) Targeting autophagy in cancer. Cancer 124:3307\u20133318. https:\/\/doi.org\/10.1002\/cncr.31335","journal-title":"Cancer"},{"key":"1655_CR22","doi-asserted-by":"publisher","first-page":"e2807","DOI":"10.1038\/cddis.2017.217","volume":"8","author":"L Wang","year":"2017","unstructured":"Wang L, Gundelach JH, Bram RJ (2017) Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme. Cell Death Dis 8:e2807. https:\/\/doi.org\/10.1038\/cddis.2017.217","journal-title":"Cell Death Dis"},{"issue":"6","key":"1655_CR23","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1096\/fj.10-175158","volume":"25","author":"Y Tian","year":"2011","unstructured":"Tian Y, Bustos V, Flajolet M, Greengard P (2011) A small-molecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway. FASEB J 25(6):1934\u20131942. https:\/\/doi.org\/10.1096\/fj.10-175158","journal-title":"FASEB J"},{"key":"1655_CR24","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nchembio883","volume":"3","author":"S Sarkar","year":"2007","unstructured":"Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL, Webster JA, Lewis TA, O\u2019Kane CJ, Schreiber SL, Rubinsztein DC (2007) Small molecules enhance autophagy and reduce toxicity in Huntington\u2019s disease models. Nat Chem Biol 3:331\u2013338. https:\/\/doi.org\/10.1038\/nchembio883","journal-title":"Nat Chem Biol"},{"key":"1655_CR25","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1007\/s10637-018-0566-0","volume":"36","author":"MI Koukourakis","year":"2018","unstructured":"Koukourakis MI, Giatromanolaki A, Fylaktakidou K, Sivridis E, Zois CE, Kalamida D, Mitrakas A, Pouliliou S, Karagounis IV, Simopoulos K, Ferguson DJP, Harris AL (2018) SMER28 is a mTOR-independent small molecule enhancer of autophagy that protects mouse bone marrow and liver against radiotherapy. Invest New Drugs 36:773\u2013781. https:\/\/doi.org\/10.1007\/s10637-018-0566-0","journal-title":"Invest New Drugs"},{"issue":"2","key":"1655_CR26","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41419-017-0018-3","volume":"9","author":"T Li","year":"2018","unstructured":"Li T, Ma R, Zhang Y, Mo H, Yang X, Hu S, Wang L, Novakovic VA, Chen H, Kou J, Bi Y, Yu B, Fang S, Wang J, Zhou J, Shi J (2018) Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy. Cell Death Dis 9(2):75. https:\/\/doi.org\/10.1038\/s41419-017-0018-3","journal-title":"Cell Death Dis"},{"key":"1655_CR27","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.freeradbiomed.2017.02.015","volume":"106","author":"G Wang","year":"2017","unstructured":"Wang G, Zhang T, Sun W, Wang H, Yin F, Wang Z, Zuo D, Sun M, Zhou Z, Lin B, Xu J, Hua Y, Li H, Cai Z (2017) Arsenic sulfide induces apoptosis and autophagy through the activation of ROS\/JNK and suppression of Akt\/mTOR signaling pathways in osteosarcoma. Free Radic Biol Med 106:24\u201337. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2017.02.015","journal-title":"Free Radic Biol Med"},{"key":"1655_CR28","doi-asserted-by":"publisher","first-page":"e457","DOI":"10.1038\/cddis.2012.192","volume":"4","author":"PK Singha","year":"2013","unstructured":"Singha PK, Pandeswara S, Venkatachalam MA, Saikumar P (2013) Manumycin A inhibits triple-negative breast cancer growth through LC3-mediated cytoplasmic vacuolation death. Cell Death Dis 4:e457. https:\/\/doi.org\/10.1038\/cddis.2012.192","journal-title":"Cell Death Dis"},{"key":"1655_CR29","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.phrs.2019.04.004","volume":"144","author":"K Banik","year":"2019","unstructured":"Banik K, Ranaware AM, Deshpande V, Nalawade SP, Padmavathi G, Bordoloi D, Sailo BL, Shanmugam MK, Fan L, Arfuso F, Sethi G, Kunnumakkara AB (2019) Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets. Pharmacol Res 144:192\u2013209. https:\/\/doi.org\/10.1016\/j.phrs.2019.04.004","journal-title":"Pharmacol Res"},{"key":"1655_CR30","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1300874","volume":"369","author":"F Lo-Coco","year":"2013","unstructured":"Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, L\u00fcbbert M, H\u00e4nel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, D\u00f6hner K, Sauer M, Ganser A, Amadori S, Mandelli F, D\u00f6hner H, Ehninger G, Schlenk RF, Platzbecker U, Gruppo Italiano Malattie Ematologiche dell\u2019Adulto, German-Austrian Acute Myeloid Leukemia Study Group, Study Alliance Leukemia (2013) Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369:111\u2013121. https:\/\/doi.org\/10.1056\/NEJMoa1300874","journal-title":"N Engl J Med"},{"key":"1655_CR31","doi-asserted-by":"publisher","first-page":"448","DOI":"10.3390\/ijms19020448","volume":"19","author":"CM Pfeffer","year":"2018","unstructured":"Pfeffer CM, Singh ATK (2018) Apoptosis: a target for anticancer therapy. Int J Mol Sci 19:448. https:\/\/doi.org\/10.3390\/ijms19020448","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1655_CR32","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/ijms19010132","volume":"19","author":"P Chlapek","year":"2018","unstructured":"Chlapek P, Slavikova V, Mazanek P, Sterba J, Veselska R (2018) Why differentiation therapy sometimes fails: molecular mechanisms of resistance to retinoids. Int J Mol Sci 19(1):132. https:\/\/doi.org\/10.3390\/ijms19010132","journal-title":"Int J Mol Sci"},{"key":"1655_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201702446","author":"Y Zhou","year":"2018","unstructured":"Zhou Y, Huang F, Yang Y, Wang P, Zhang Z, Tang Y, Shen Y, Wang K (2018) Paraptosis-inducing nanomedicine overcomes cancer drug resistance for a potent cancer therapy. Small. https:\/\/doi.org\/10.1002\/smll.201702446","journal-title":"Small"},{"key":"1655_CR34","doi-asserted-by":"publisher","first-page":"188338","DOI":"10.1016\/j.bbcan.2020.188338","volume":"1873","author":"F Fontana","year":"2020","unstructured":"Fontana F, Raimondi M, Marzagalli M, Di Domizio A, Limonta P (2020) The emerging role of paraptosis in tumor cell biology: Perspectives for cancer prevention and therapy with natural compounds. Biochim Biophys Acta Rev Cancer 1873:188338. https:\/\/doi.org\/10.1016\/j.bbcan.2020.188338","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"1655_CR35","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1038\/sj.cdd.4401465","volume":"11","author":"S Sperandio","year":"2004","unstructured":"Sperandio S, Poksay K, de Belle I, Lafuente MJ, Liu B, Nasir J, Bredesen DE (2004) Paraptosis: mediation by MAP kinases and inhibition by AIP-1\/Alix. Cell Death Differ 11:1066\u20131075. https:\/\/doi.org\/10.1038\/sj.cdd.4401465","journal-title":"Cell Death Differ"},{"issue":"9","key":"1655_CR36","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1007\/s00432-017-2464-9","volume":"143","author":"MH Raza","year":"2017","unstructured":"Raza MH, Siraj S, Arshad A, Waheed U, Aldakheel F, Alduraywish S, Arshad M (2017) ROS-modulated therapeutic approaches in cancer treatment. J Cancer Res Clin Oncol 143(9):1789\u20131809. https:\/\/doi.org\/10.1007\/s00432-017-2464-9","journal-title":"J Cancer Res Clin Oncol"},{"key":"1655_CR37","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.3892\/or.2020.7576","volume":"43","author":"C Wang","year":"2020","unstructured":"Wang C, Li TK, Zeng CH, Fan R, Wang Y, Zhu GY, Guo JH (2020) Iodine-125 seed radiation induces ROS-mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells. Oncol Rep 43:2028\u20132044. https:\/\/doi.org\/10.3892\/or.2020.7576","journal-title":"Oncol Rep"},{"issue":"12","key":"1655_CR38","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1002\/jcp.25349","volume":"231","author":"Y Yang","year":"2016","unstructured":"Yang Y, Karakhanova S, Hartwig W, D\u2019Haese JG, Philippov PP, Werner J, Bazhin AV (2016) Mitochondria and mitochondrial ROS in cancer: novel targets for anticancer therapy. J Cell Physiol 231(12):2570\u20132581. https:\/\/doi.org\/10.1002\/jcp.25349","journal-title":"J Cell Physiol"},{"key":"1655_CR39","doi-asserted-by":"publisher","first-page":"6942","DOI":"10.1039\/c8dt00783g","volume":"47","author":"L He","year":"2018","unstructured":"He L, Wang KN, Zheng Y, Cao JJ, Zhang MF, Tan CP, Ji LN, Mao ZW (2018) Cyclometalated iridium(iii) complexes induce mitochondria-derived paraptotic cell death and inhibit tumor growth in vivo. Dalton Trans 47:6942\u20136953. https:\/\/doi.org\/10.1039\/c8dt00783g","journal-title":"Dalton Trans"},{"key":"1655_CR40","doi-asserted-by":"publisher","first-page":"9566","DOI":"10.1038\/s41598-018-27724-3","volume":"8","author":"H Han","year":"2018","unstructured":"Han H, Chou CC, Li R, Liu J, Zhang L, Zhu W, Hu J, Yang B, Tian J (2018) Chalcomoracin is a potent anticancer agent acting through triggering Oxidative stress via a mitophagy- and paraptosis-dependent mechanism. Sci Rep 8:9566. https:\/\/doi.org\/10.1038\/s41598-018-27724-3","journal-title":"Sci Rep"},{"key":"1655_CR41","doi-asserted-by":"publisher","first-page":"108733","DOI":"10.1016\/j.cbi.2019.108733","volume":"310","author":"A Binoy","year":"2019","unstructured":"Binoy A, Nedungadi D, Katiyar N, Bose C, Shankarappa SA, Nair BG, Mishra N (2019) Plumbagin induces paraptosis in cancer cells by disrupting the sulfhydryl homeostasis and proteasomal function. Chem Biol Interact 310:108733. https:\/\/doi.org\/10.1016\/j.cbi.2019.108733","journal-title":"Chem Biol Interact"},{"key":"1655_CR42","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41419-019-1360-4","volume":"10","author":"MJ Seo","year":"2019","unstructured":"Seo MJ, Lee DM, Kim IY, Lee D, Choi MK, Lee JY, Park SS, Jeong SY, Choi EK, Choi KS (2019) Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis. Cell Death Dis 10:187. https:\/\/doi.org\/10.1038\/s41419-019-1360-4","journal-title":"Cell Death Dis"},{"key":"1655_CR43","doi-asserted-by":"publisher","first-page":"e12576","DOI":"10.1111\/cpr.12576","volume":"52","author":"F Fontana","year":"2019","unstructured":"Fontana F, Moretti RM, Raimondi M, Marzagalli M, Beretta G, Procacci P, Sartori P, Montagnani Marelli M, Limonta P (2019) \u03b4-Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells. Cell Prolif 52:e12576. https:\/\/doi.org\/10.1111\/cpr.12576","journal-title":"Cell Prolif"}],"container-title":["Apoptosis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-020-01655-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10495-020-01655-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-020-01655-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T10:38:10Z","timestamp":1617273490000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10495-020-01655-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,7]]},"references-count":43,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["1655"],"URL":"https:\/\/doi.org\/10.1007\/s10495-020-01655-9","relation":{},"ISSN":["1360-8185","1573-675X"],"issn-type":[{"value":"1360-8185","type":"print"},{"value":"1573-675X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,7]]},"assertion":[{"value":"29 December 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}