{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:34:08Z","timestamp":1769124848989,"version":"3.49.0"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T00:00:00Z","timestamp":1439251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81000938"],"award-info":[{"award-number":["81000938"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Melatonin is an indoleamine synthesized in the pineal gland that shows a wide range of physiological and pharmacological functions, including anticancer effects. In this study, we investigated the effect of melatonin on drug\u2010induced cellular apoptosis against the cultured human lung adenocarcinoma cells and explored the role of histone deacetylase (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>) signaling in this process. The results showed that melatonin treatment led to a dose\u2010 and time\u2010dependent decrease in the viability of human A549 and <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>9 lung adenocarcinoma cells. Additionally, melatonin exhibited potent anticancer activity in\u00a0vitro, as evidenced by reductions of the cell adhesion, migration, and the intracellular glutathione (<jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>) level and increases in the apoptotic index, caspase 3 activity, and reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) in A549 and <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>9 cells. Melatonin treatment also influenced the expression of <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\u2010related molecules (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>1 and Ac\u2010histone H3), upregulated the apoptosis\u2010related molecules (<jats:styled-content style=\"fixed-case\">PUMA<\/jats:styled-content> and Bax), and downregulated the proliferation\u2010related molecule (<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>) and the anti\u2010apoptosis\u2010related molecule (Bcl2). Furthermore, the inhibition of <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> signaling using <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>1 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">SAHA<\/jats:styled-content> (a potent pan\u2010inhibitor of <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s) sensitized A549 and <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>9 cells to the melatonin treatment. In summary, these data indicate that in\u00a0vitro\u2010administered melatonin is a potential suppressor of lung adenocarcinoma cells by the targeting of <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> signaling and suggest that melatonin in combination with <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> inhibitors may be a novel therapeutic intervention for human lung adenocarcinoma.<\/jats:p>","DOI":"10.1111\/jpi.12261","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T15:45:14Z","timestamp":1437061514000},"page":"321-333","source":"Crossref","is-referenced-by-count":54,"title":["Retracted: <scp>HDAC<\/scp>1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways"],"prefix":"10.1111","volume":"59","author":[{"given":"Chongxi","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine The 92nd Hospital of PLA Nanping China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shouyin","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Aerospace Medicine The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weimiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology UT Health Science Center San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2013.0084"},{"issue":"5","key":"e_1_2_7_4_1","first-page":"S463","article-title":"The pivotal role of pathology in the management of lung cancer","volume":"5","author":"Davidson MR","year":"2013","journal-title":"J Thor Dis"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.8126"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.12.024"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.1228"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12162"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12090"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12176"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00940.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2012.00974.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2012.01006.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12140"},{"key":"e_1_2_7_15_1","first-page":"513","article-title":"Effect of melatonin on cytotoxicity of doxorubicin toward selected cell lines (human keratinocytes, lung cancer cell line A\u2010549, laryngeal cancer cell line Hep\u20102)","volume":"21","author":"Fic M","year":"2007","journal-title":"In Vivo"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12158"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200316"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.1291"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.11.003"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.02.012"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7310149"},{"key":"e_1_2_7_22_1","first-page":"769","article-title":"Expression profile of class I histone deacetylases in human cancer tissues","volume":"18","author":"Nakagawa M","year":"2007","journal-title":"Oncol Rep"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1150"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1779"},{"key":"e_1_2_7_25_1","first-page":"4460","article-title":"Novel mechanisms of apoptosis induced by histone deacetylase inhibitors","volume":"63","author":"Peart MJ","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.267"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2013.729042"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.01.022"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12226"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.05.017"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6058"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.25664"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00600.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083699"},{"key":"e_1_2_7_35_1","first-page":"1497","article-title":"Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, suppresses the growth of carcinogen\u2010induced mammary tumors","volume":"22","author":"Cohen LA","year":"2002","journal-title":"Anticancer Res"},{"key":"e_1_2_7_36_1","first-page":"5165","article-title":"Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in\u00a0vitro and in\u00a0vivo","volume":"60","author":"Butler LM","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3149"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(84)90007-4"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366305"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101132"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2012.737805"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12205"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12131"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00823.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.0860"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2012.07.007"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20022"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-08-450916"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-461988"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-441949"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1322"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80430-4"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4839"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2658"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2015.02.003"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092627"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370605"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.353201"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(200101)46:1<52::AID-PROS1008>3.0.CO;2-Z"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2799"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2978-6"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyu105"}],"updated-by":[{"DOI":"10.1111\/jpi.12612","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T00:00:00Z","timestamp":1571356800000},"record-id":"21456"},{"DOI":"10.1111\/jpi.12612","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T00:00:00Z","timestamp":1571356800000}}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjpi.12261","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjpi.12261","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12261","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.12261","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12261","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T09:37:53Z","timestamp":1694252273000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,11]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/jpi.12261"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12261","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,11]]}}}