{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:40:14Z","timestamp":1786995614416,"version":"build-2736575974"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012465","name":"Zunyi Medical College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012465","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2024,5]]},"DOI":"10.1016\/j.phymed.2024.155391","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T03:51:27Z","timestamp":1708487487000},"page":"155391","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"special_numbering":"C","title":["Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC\/Nrf2 axis"],"prefix":"10.1016","volume":"127","author":[{"given":"Mei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-1148","authenticated-orcid":false,"given":"Limin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2024.155391_bib0001","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.freeradbiomed.2018.07.014","article-title":"Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability","volume":"126","author":"Afrin","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.phymed.2024.155391_bib0002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0132978","article-title":"The Crosstalk between Nrf2 and TGF-beta1 in the epithelial-mesenchymal transition of pancreatic duct epithelial cells","volume":"10","author":"Arfmann-Knubel","year":"2015","journal-title":"PLoS. One"},{"key":"10.1016\/j.phymed.2024.155391_bib0003","doi-asserted-by":"crossref","first-page":"998","DOI":"10.2174\/18735592MTEx9NTk2y","article-title":"Colorectal cancer epidemiology: recent trends and impact on outcomes","volume":"22","author":"Baidoun","year":"2021","journal-title":"Curr. Drug Targets."},{"key":"10.1016\/j.phymed.2024.155391_bib0004","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41580-020-0215-2","article-title":"Target gene-independent functions of MYC oncoproteins","volume":"21","author":"Baluapuri","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.phymed.2024.155391_bib0005","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.ccell.2021.03.004","article-title":"Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver","volume":"39","author":"Bertocchi","year":"2021","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phymed.2024.155391_bib0007","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.phrs.2017.07.009","article-title":"Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating beta-catenin","volume":"123","author":"Chen","year":"2017","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phymed.2024.155391_bib0008","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.phrs.2017.09.016","article-title":"Reflection on the selection of doses of arenobufagin in vivo anticancer study","volume":"128","author":"Chen","year":"2018","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phymed.2024.155391_bib0009","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1158\/2159-8290.CD-13-0346","article-title":"RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant metastasis","volume":"4","author":"Cho","year":"2014","journal-title":"Cancer Discov."},{"key":"10.1016\/j.phymed.2024.155391_bib0010","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1124\/jpet.110.170555","article-title":"In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc\/Max dimerization","volume":"335","author":"Clausen","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.phymed.2024.155391_bib0011","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1101\/gad.231894.113","article-title":"Stress-induced cleavage of Myc promotes cancer cell survival","volume":"28","author":"Conacci-Sorrell","year":"2014","journal-title":"Genes Dev."},{"key":"10.1016\/j.phymed.2024.155391_bib0012","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41568-020-00329-7","article-title":"The matrix in cancer","volume":"21","author":"Cox","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.phymed.2024.155391_bib0013","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature10189","article-title":"Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis","volume":"475","author":"DeNicola","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.phymed.2024.155391_bib0014","article-title":"Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C\/3L transformation","volume":"117","author":"Gong","year":"2023","journal-title":"Phytomed"},{"key":"10.1016\/j.phymed.2024.155391_bib0015","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ccell.2019.10.001","article-title":"Small-molecule MYC inhibitors suppress tumor growth and enhance immunotherapy","volume":"36","author":"Han","year":"2019","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phymed.2024.155391_bib0016","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12032-020-01419-0","article-title":"The DPP-IV inhibitor saxagliptin promotes the migration and invasion of papillary thyroid carcinoma cells via the NRF2\/HO1 pathway","volume":"37","author":"He","year":"2020","journal-title":"Med. Oncol."},{"key":"10.1016\/j.phymed.2024.155391_bib0017","doi-asserted-by":"crossref","first-page":"e973","DOI":"10.1002\/ctm2.973","article-title":"Identification of BGN and THBS2 as metastasis-specific biomarkers and poor survival key regulators in human colon cancer by integrated analysis","volume":"12","author":"He","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.phymed.2024.155391_bib0018","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature14985","article-title":"The spliceosome is a therapeutic vulnerability in MYC-driven cancer","volume":"525","author":"Hsu","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.phymed.2024.155391_bib0019","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13046-019-1135-x","article-title":"MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS\/Nrf2\/Notch pathway in hepatocellular carcinoma","volume":"38","author":"Jin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.phymed.2024.155391_bib0020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2000784","article-title":"Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1","volume":"15","author":"Juneja","year":"2017","journal-title":"PLoS. Biol."},{"key":"10.1016\/j.phymed.2024.155391_bib0021","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1158\/0008-5472.CAN-21-0453","article-title":"Fusobacterium nucleatum promotes the development of colorectal cancer by activating a cytochrome P450\/epoxyoctadecenoic acid axis via TLR4\/Keap1\/NRF2 signaling","volume":"81","author":"Kong","year":"2021","journal-title":"Cancer Res."},{"key":"10.1016\/j.phymed.2024.155391_bib0022","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.bcp.2012.01.023","article-title":"Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathway","volume":"83","author":"Li","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2024.155391_bib0023","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s12967-023-04120-8","article-title":"Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt\/\u03b2-catenin\/c-Myc\/SOX2 pathway in colorectal cancer","volume":"21","author":"Li","year":"2023","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.phymed.2024.155391_bib0024","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cell.2019.06.003","article-title":"Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1","volume":"178","author":"Lignitto","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.phymed.2024.155391_bib0025","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00109-016-1452-x","article-title":"C-myc overexpression drives melanoma metastasis by promoting vasculogenic mimicry via c-myc\/snail\/Bax signaling","volume":"95","author":"Lin","year":"2017","journal-title":"J. Mol. Med. (Berl)"},{"key":"10.1016\/j.phymed.2024.155391_bib0026","article-title":"Nrf2 down-regulation by camptothecin favors inhibiting invasion, metastasis and angiogenesis in hepatocellular carcinoma","volume":"11","author":"Liu","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.phymed.2024.155391_bib0027","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/neuonc\/nos262","article-title":"Osteopontin increases heme oxygenase-1 expression and subsequently induces cell migration and invasion in glioma cells","volume":"14","author":"Lu","year":"2012","journal-title":"Neuro. Oncol."},{"key":"10.1016\/j.phymed.2024.155391_bib0028","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.2147\/OTT.S104767","article-title":"Arenobufagin activates p53 to trigger esophageal squamous cell carcinoma cell apoptosis in vitro and in vivo","volume":"10","author":"Lv","year":"2017","journal-title":"Onco. Targets. Ther."},{"key":"10.1016\/j.phymed.2024.155391_bib0029","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.3390\/molecules22091525","article-title":"Arenobufagin induces apoptotic cell death in human non-small-cell lung cancer cells via the noxa-related pathway","volume":"22","author":"Ma","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.phymed.2024.155391_bib0030","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.3390\/cells9092133","article-title":"NRF2 Is an upstream regulator of MYC-mediated osteoclastogenesis and pathological bone erosion","volume":"9","author":"Park","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.phymed.2024.155391_bib0031","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1101\/gad.344184.120","article-title":"ATDC binds to KEAP1 to drive NRF2-mediated tumorigenesis and chemoresistance in pancreatic cancer","volume":"35","author":"Purohit","year":"2021","journal-title":"Genes Dev."},{"key":"10.1016\/j.phymed.2024.155391_bib0032","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.104625","article-title":"A newly identified small molecular compound acts as a protein kinase inhibitor to suppress metastasis of colorectal cancer","volume":"107","author":"Qi","year":"2021","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.phymed.2024.155391_bib0033","doi-asserted-by":"crossref","first-page":"e6029","DOI":"10.1371\/journal.pone.0006029","article-title":"MYC is a metastasis gene for non-small-cell lung cancer","volume":"4","author":"Rapp","year":"2009","journal-title":"PLoS. One"},{"key":"10.1016\/j.phymed.2024.155391_bib0034","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the hallmarks of cancer","volume":"34","author":"Rojo de la Vega","year":"2018","journal-title":"Cancer Cell"},{"issue":"19","key":"10.1016\/j.phymed.2024.155391_bib0035","doi-asserted-by":"crossref","first-page":"11263","DOI":"10.3390\/ijms231911263","article-title":"Proviral ALV-LTR sequence is essential for continued proliferation of the ALV-transformed B cell line","volume":"23","author":"Roy","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2024.155391_bib0036","doi-asserted-by":"crossref","first-page":"5232","DOI":"10.7150\/thno.53417","article-title":"c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation","volume":"11","author":"Tang","year":"2021","journal-title":"Theranostics."},{"key":"10.1016\/j.phymed.2024.155391_bib0037","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2015.06.021","article-title":"Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease","volume":"88","author":"Tebay","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.phymed.2024.155391_bib0038","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1080\/21541248.2017.1364821","article-title":"MYC leads the way","volume":"11","author":"Venkateswaran","year":"2020","journal-title":"Small. GTPases."},{"key":"10.1016\/j.phymed.2024.155391_bib0039","first-page":"334ra351","article-title":"NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis","volume":"8","author":"Wang","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.phymed.2024.155391_bib0040","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/9742154","article-title":"UVA irradiation enhances brusatol-mediated inhibition of melanoma growth by downregulation of the Nrf2-mediated antioxidant response","volume":"2018","author":"Wang","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"10.1016\/j.phymed.2024.155391_bib0041","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/MPA.0000000000001471","article-title":"Arenobufagin inhibits the phosphatidylinositol 3-kinase\/protein kinase B\/mammalian target of rapamycin pathway and induces apoptosis and autophagy in pancreatic cancer cells","volume":"49","author":"Wei","year":"2020","journal-title":"Pancreas."},{"key":"10.1016\/j.phymed.2024.155391_bib0042","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2021.113004","article-title":"Numb inhibits migration and promotes proliferation of colon cancer cells via RhoA\/ROCK signaling pathway repression","volume":"411","author":"Yang","year":"2022","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.phymed.2024.155391_bib0043","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.2147\/IJN.S139128","article-title":"Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles","volume":"12","author":"Yuan","year":"2017","journal-title":"Int J Nanomed"},{"key":"10.1016\/j.phymed.2024.155391_bib0044","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1111\/jcmm.14241","article-title":"Nrf2 promotes breast cancer cell migration via up-regulation of G6PD\/HIF-1\u03b1\/Notch1 axis","volume":"23","author":"Zhang","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.phymed.2024.155391_bib0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.112943","article-title":"The lipid homeostasis regulation study of arenobufagin in zebrafish HepG2 xenograft model and HepG2 cells using integrated lipidomics-proteomics approach","volume":"260","author":"Zhao","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2024.155391_bib0046","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1006\/bbrc.2001.5944","article-title":"Functional characterization of transcription regulators that interact with the electrophile response element","volume":"289","author":"Zhu","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711324000564?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711324000564?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:54:44Z","timestamp":1760554484000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711324000564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":45,"alternative-id":["S0944711324000564"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2024.155391","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC\/Nrf2 axis","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2024.155391","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"155391"}}