{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:08:18Z","timestamp":1790251698529,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T00:00:00Z","timestamp":1534896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006368","name":"Universidad de Las Palmas de Gran Canaria","doi-asserted-by":"publisher","award":["ULPGC2009\u201014"],"award-info":[{"award-number":["ULPGC2009\u201014"]}],"id":[{"id":"10.13039\/501100006368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Photodynamic therapy (PDT) is a rising and hopeful treatment for solid tumors and others malignancies. PDT uses harmless visible light to activate a tumor\u2010associated photosensitizer (PS). The excited PS generates cytotoxic reactive oxygen species (ROS) that induce damage and death of tumor cells. It is known that certain phytoalexins and phytoanticipins derived from plants often display a PS\u2010like activity due to a phenalenone (PN) moiety\u2014an efficient singlet oxygen photosensitizer\u2014in its skeleton. The aim of this study is to explore the phototoxic properties of PN on the human cell line tumor\u2010derived HL60 (acute promyelocytic leukemia) and to identify the cell\u2010specific targets of ROS involved in the tumor cell death. Our results reveal that PN acts as an excellent PS, showing a potent antitumor cell activity in presence of light. PN\u2010PDT generates intracellular ROS, via oxidation reaction mechanisms type I and II, resulting in an induction of apoptosis. Moreover, both extrinsic (through direct activation of caspase\u20103) and intrinsic (through mitochondrial depolarization) pathways of apoptosis are induced by PN\u2010PDT. Using pharmacologic inhibitors, we also find that PN\u2010PDT activates caspase\u20108\/tBid and p38\u2010MAPK, triggering the activation of the apoptotic pathways. Although, survival pathways are also promoted through PI3\u2009K\/Akt and JNK activation, the net result of PN\u2010PDT is the tumor cell death. The present work identifies to PN, for the first time, as a potent photosensitizer in human tumor cell lines and proposes a mechanism by which ROS induces apoptosis of tumor cell.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22875","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T11:17:31Z","timestamp":1532344651000},"page":"1525-1539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Phenalenone\u2010photodynamic therapy induces apoptosis on human tumor cells mediated by caspase\u20108 and p38\u2010MAPK activation"],"prefix":"10.1002","volume":"57","author":[{"given":"Mar\u00eda L.","family":"Salmer\u00f3n","sequence":"first","affiliation":[{"name":"Facultad de Ciencias, Departamento de Ciencias y Recursos Naturales Universidad de Magallanes Punta Arenas Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Quintana\u2010Aguiar","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular Fisiolog\u00eda, Gen\u00e9tica e Inmunolog\u00eda. Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS) Universidad de Las Palmas de Gran Canaria Las Palmas Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan V.","family":"De La Rosa","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina Asociada al Consejo Superior de Investigaciones Cient\u00edficas (Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC\u2010Universidad Aut\u00f3noma de Madrid), Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Grupo de Investigaci\u00f3n Medio Ambiente y Salud (GIMAS) Universidad de las Palmas de Gran Canaria Las Palmas Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix","family":"L\u00f3pez\u2010Blanco","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina Asociada al Consejo Superior de Investigaciones Cient\u00edficas (Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC\u2010Universidad Aut\u00f3noma de Madrid), Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Grupo de Investigaci\u00f3n Medio Ambiente y Salud (GIMAS) Universidad de las Palmas de Gran Canaria Las Palmas Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Castrillo","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina Asociada al Consejo Superior de Investigaciones Cient\u00edficas (Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC\u2010Universidad Aut\u00f3noma de Madrid), Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Grupo de Investigaci\u00f3n Medio Ambiente y Salud (GIMAS) Universidad de las Palmas de Gran Canaria Las Palmas Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germ\u00e1n","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina Asociada al Consejo Superior de Investigaciones Cient\u00edficas (Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC\u2010Universidad Aut\u00f3noma de Madrid), Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Grupo de Investigaci\u00f3n Medio Ambiente y Salud (GIMAS) Universidad de las Palmas de Gran Canaria Las Palmas Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-8116","authenticated-orcid":false,"given":"Carlos","family":"Tabraue","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina Asociada al Consejo Superior de Investigaciones Cient\u00edficas (Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC\u2010Universidad Aut\u00f3noma de Madrid), Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Grupo de Investigaci\u00f3n Medio Ambiente y Salud (GIMAS) Universidad de las Palmas de Gran Canaria Las Palmas Spain"},{"name":"Departamento de Morfolog\u00eda Universidad de Las Palmas de Gran Canaria Las Palmas Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.12.889"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12857"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1991.tb02071.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3022516"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1894"},{"key":"e_1_2_7_7_1","first-page":"765","article-title":"Targeting of the vascular system of solid tumours by photodynamic therapy (PDT)","volume":"3","author":"Abels C","year":"2004","journal-title":"Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/b108586g"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2004.05.003"},{"key":"e_1_2_7_10_1","first-page":"257","article-title":"Photodynamic therapy induced Fas\u2010mediated apoptosis in human carcinoma cells","volume":"9","author":"Ali SM","year":"2002","journal-title":"Int J Mol Med"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612053507648"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2007.07.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400558"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.02.029"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2009.04.001"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.12.889"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma6030817"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/1010-6030(93)03746-4"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/1010-6030(96)04321-3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9422(96)00796-0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/50700974"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3np70088g"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/B401294A"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.04.062"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2013.08.008"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1314168110"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42058"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm4019492"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpca.6b03615"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715761003709802"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bio.867"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/bio.1296"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4078"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.268946"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.12.022"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.08.021"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.96"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/1010-6030(96)04321-3"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00982-6"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpca.6b03615"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02268-2"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.179"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001185200"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1736"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-011-1165-5"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1572-1000(05)00030-X"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.6.2118-2129.2006"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510644200"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.10.031"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8788"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2007.00137.x"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.05.025"},{"key":"e_1_2_7_53_1","first-page":"159","article-title":"Critical role of bad phosphorylation by Akt in cytostatic resistance of human bladder cancer cells","volume":"29","author":"Szanto A","year":"2009","journal-title":"Anticancer Res"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2007.00137.x"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.508994"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081056"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15098"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(02)02164-7"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2013.2220"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.meg.0000223910.08611.79"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22875","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22875","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mc.22875","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T22:11:09Z","timestamp":1694124669000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.22875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,22]]},"references-count":59,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/mc.22875"],"URL":"https:\/\/doi.org\/10.1002\/mc.22875","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,22]]},"assertion":[{"value":"2018-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}