{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:09:11Z","timestamp":1790190551092,"version":"4.1.0"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20374"],"award-info":[{"award-number":["U22A20374"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972291"],"award-info":[{"award-number":["81972291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060434"],"award-info":[{"award-number":["82060434"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32160160"],"award-info":[{"award-number":["32160160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1016\/j.phymed.2023.155089","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:29:55Z","timestamp":1694748595000},"page":"155089","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair"],"prefix":"10.1016","volume":"121","author":[{"given":"Xin-Yu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Quan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Di","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Ru","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Lian","family":"Bin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Yun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-9670","authenticated-orcid":false,"given":"Cheng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Huan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6056-3196","authenticated-orcid":false,"given":"Guo-Dong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2475-7783","authenticated-orcid":false,"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2023.155089_bib0001","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1158\/0008-5472.CAN-22-2065","article-title":"p53 activation paradoxically causes liver cancer","volume":"82","author":"Barton","year":"2022","journal-title":"Cancer Res."},{"key":"10.1016\/j.phymed.2023.155089_bib0002","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2019.100671","article-title":"Towards the overcoming of anticancer drug resistance mediated by p53 mutations","volume":"49","author":"Cao","year":"2020","journal-title":"Drug Resist. Updat."},{"key":"10.1016\/j.phymed.2023.155089_bib0003","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/14728222.2019.1601703","article-title":"Sequestosome 1\/p62-related pathways as therapeutic targets in hepatocellular carcinoma","volume":"23","author":"Denk","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.phymed.2023.155089_bib0004","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/path.1946","article-title":"Are the Mallory bodies and intracellular hyaline bodies in neoplastic and non-neoplastic hepatocytes related?","volume":"208","author":"Denk","year":"2006","journal-title":"J. Pathol."},{"key":"10.1016\/j.phymed.2023.155089_bib0005","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ccr.2008.02.001","article-title":"The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis","volume":"13","author":"Duran","year":"2008","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phymed.2023.155089_bib0006","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41401-020-0439-x","article-title":"ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma","volume":"42","author":"Feng","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.phymed.2023.155089_bib0007","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41573-022-00571-8","article-title":"Drugging p53 in cancer: one protein, many targets","volume":"22","author":"Hassin","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.phymed.2023.155089_bib0008","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1016\/j.cell.2022.10.004","article-title":"Enhanced DNA repair through droplet formation and p53 oscillations","volume":"185","author":"Heltberg","year":"2022","journal-title":"Cell"},{"key":"10.1016\/j.phymed.2023.155089_bib0009","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.molcel.2013.08.003","article-title":"Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy","volume":"51","author":"Ichimura","year":"2013","journal-title":"Mol. Cell"},{"key":"10.1016\/j.phymed.2023.155089_bib0010","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1083\/jcb.201102031","article-title":"Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells","volume":"193","author":"Inami","year":"2011","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.phymed.2023.155089_bib0011","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.canlet.2018.01.074","article-title":"'Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer'","volume":"420","author":"Islam","year":"2018","journal-title":"Cancer Lett."},{"key":"10.1016\/j.phymed.2023.155089_bib0012","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1111\/bph.15080","article-title":"Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease","volume":"177","author":"Liao","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.phymed.2023.155089_bib0013","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1073\/pnas.1409563112","article-title":"Loss of autophagy causes a synthetic lethal deficiency in DNA repair","volume":"112","author":"Liu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.phymed.2023.155089_bib0014","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms9122561","article-title":"Andrographolide inhibits lytic reactivation of epstein-barr virus by modulating transcription factors in gastric cancer","volume":"9","author":"Malat","year":"2021","journal-title":"Microorganisms"},{"key":"10.1016\/j.phymed.2023.155089_bib0015","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s13046-018-0926-9","article-title":"Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway","volume":"37","author":"Peng","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.phymed.2023.155089_bib0016","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cbi.2017.06.024","article-title":"Andrographolide reduced VEGFA expression in hepatoma cancer cells by inactivating HIF-1alpha: the involvement of JNK and MTA1\/HDCA","volume":"273","author":"Shi","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.phymed.2023.155089_bib0017","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.phymed.2023.155089_bib0018","article-title":"Metabolism-based molecular subtyping endows effective ketogenic therapy in p53-mutant colon cancer","volume":"9","author":"Tang","year":"2022","journal-title":"Adv. Sci. (Weinh.)"},{"key":"10.1016\/j.phymed.2023.155089_bib0019","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.ccell.2016.04.006","article-title":"'p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells'","volume":"29","author":"Umemura","year":"2016","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phymed.2023.155089_bib0020","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nrgastro.2012.199","article-title":"Medical therapies for hepatocellular carcinoma: a critical view of the evidence","volume":"10","author":"Villanueva","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.phymed.2023.155089_bib0021","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1074\/mcp.M113.029793","article-title":"A quantitative chemical proteomics approach to profile the specific cellular targets of andrographolide, a promising anticancer agent that suppresses tumor metastasis","volume":"13","author":"Wang","year":"2014","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.phymed.2023.155089_bib0022","article-title":"Shen Shuai II recipe attenuates apoptosis in 5\/6 renal ablation\/infarction rats by inhibiting p53 and the mitochondrial pathway of apoptosis","volume":"2020","author":"Wang","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"10.1016\/j.phymed.2023.155089_bib0023","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.molcel.2016.05.027","article-title":"Autophagy regulates chromatin ubiquitination in DNA damage response through elimination of SQSTM1\/p62","volume":"63","author":"Wang","year":"2016","journal-title":"Mol. Cell"},{"key":"10.1016\/j.phymed.2023.155089_bib0024","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/bph.15350","article-title":"Quercetin induces p53-independent cancer cell death through lysosome activation by the transcription factor EB and Reactive Oxygen Species-dependent ferroptosis","volume":"178","author":"Wang","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.phymed.2023.155089_bib0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2020.173470","article-title":"Andrographolide promotes skeletal muscle regeneration after acute injury through epigenetic modulation","volume":"888","author":"Wu","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phymed.2023.155089_bib0026","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1038\/s41418-022-01007-x","article-title":"Targeting the miR-34a\/LRPPRC\/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer","volume":"29","author":"Yang","year":"2022","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.phymed.2023.155089_bib0027","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115214","article-title":"Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism","volume":"292","author":"Yu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2023.155089_bib0028","first-page":"766","article-title":"Herbal formula Renshenwuweizi decoction induces p53-mediated cell cycle arrest and apoptosis in A549 cells","volume":"40","author":"Yu","year":"2020","journal-title":"J. Tradit. Chin. Med."},{"key":"10.1016\/j.phymed.2023.155089_bib0029","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0002-9440(10)64369-6","article-title":"p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases","volume":"160","author":"Zatloukal","year":"2002","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.phymed.2023.155089_bib0030","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4161\/auto.18721","article-title":"Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells","volume":"8","author":"Zhou","year":"2012","journal-title":"Autophagy"},{"key":"10.1016\/j.phymed.2023.155089_bib0031","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/s41401-018-0005-y","article-title":"Varacin-1, a novel analog of varacin C, induces p53-independent apoptosis in cancer cells through ROS-mediated reduction of XIAP","volume":"40","author":"Zhou","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.phymed.2023.155089_bib0032","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1158\/1535-7163.MCT-08-0071","article-title":"Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation","volume":"7","author":"Zhou","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.phymed.2023.155089_bib0033","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.bcp.2009.12.014","article-title":"Inhibition of the JAK-STAT3 pathway by andrographolide enhances chemosensitivity of cancer cells to doxorubicin","volume":"79","author":"Zhou","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2023.155089_bib0034","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/cr.2013.11","article-title":"Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion","volume":"23","author":"Zhou","year":"2013","journal-title":"Cell Res."},{"key":"10.1016\/j.phymed.2023.155089_bib0035","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1053\/j.gastro.2015.05.061","article-title":"Genetic landscape and biomarkers of hepatocellular carcinoma","volume":"149","author":"Zucman-Rossi","year":"2015","journal-title":"Gastroenterology"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S094471132300449X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S094471132300449X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:31:23Z","timestamp":1778776283000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S094471132300449X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":35,"alternative-id":["S094471132300449X"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2023.155089","relation":{"has-preprint":[{"id-type":"doi","id":"10.22541\/au.167844940.05342281\/v1","asserted-by":"object"}]},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2023.155089","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"155089"}}