{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:01:01Z","timestamp":1772773261372,"version":"3.50.1"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100025520","name":"Medical Research Future Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100025520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011302","name":"Children&apos;s Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011302","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001184","name":"Cure Cancer Australia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001184","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009844","name":"PA Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009844","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"State of Sao Paulo Research Foundation","doi-asserted-by":"publisher","award":["2024\/05180-1"],"award-info":[{"award-number":["2024\/05180-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"State of Sao Paulo Research Foundation","doi-asserted-by":"publisher","award":["2022\/15626-1"],"award-info":[{"award-number":["2022\/15626-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021954","name":"Tour de Cure","doi-asserted-by":"publisher","award":["QLD 4102"],"award-info":[{"award-number":["QLD 4102"]}],"id":[{"id":"10.13039\/501100021954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018675","name":"Kids&apos; Cancer Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018675","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003550","name":"Queensland Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["2019485"],"award-info":[{"award-number":["2019485"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["303350\/2022-9"],"award-info":[{"award-number":["303350\/2022-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicon"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.toxicon.2025.108501","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T23:48:45Z","timestamp":1753141725000},"page":"108501","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Antitumor activity of violacein in osteosarcoma, neuroblastoma and triple-negative breast cancer spheroids"],"prefix":"10.1016","volume":"265","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-6547","authenticated-orcid":false,"given":"Beatriz","family":"Aires-Lopes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaina","family":"Coleborn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2037-8946","authenticated-orcid":false,"given":"Fernando","family":"Souza-Fonseca-Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen Ver\u00edssima","family":"Ferreira-Halder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxicon.2025.108501_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-023-45144-w","article-title":"Comparative analysis between 2D and 3D colorectal cancer culture models for insights into cellular morphological and transcriptomic variations","volume":"13","author":"Abbas","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.toxicon.2025.108501_bib2","first-page":"19","article-title":"Violacein improves vemurafenib response in melanoma spheroids","volume":"38","author":"Aires-Lopes","year":"2023","journal-title":"Nat. Prod. Res."},{"key":"10.1016\/j.toxicon.2025.108501_bib3","author":"Aires-Lopes"},{"key":"10.1016\/j.toxicon.2025.108501_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.etp.2015.10.002","article-title":"Violacein induces apoptosis in human breast cancer cells through up regulation of BAX, p53 and down regulation of MDM2","volume":"68","author":"Alshatwi","year":"2016","journal-title":"Exp. Toxicol. Pathol."},{"key":"10.1016\/j.toxicon.2025.108501_bib5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1158\/1078-0432.CCR-21-1356","article-title":"Immunotherapy of neuroblastoma: facts and Hopes","volume":"28","author":"Anderson","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.toxicon.2025.108501_bib6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.toxicon.2025.108501_bib7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/14756360500273052","article-title":"Violacein cytotoxicity on human blood lymphocytes and effect on phosphatases","volume":"20","author":"Bromberg","year":"2005","journal-title":"J Enzyme Inhib Med Chem"},{"key":"10.1016\/j.toxicon.2025.108501_bib8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41419-024-06712-8","article-title":"Research progress on morphology and mechanism of programmed cell death","volume":"5","author":"Chen","year":"2024","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.toxicon.2025.108501_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.872223","article-title":"Characterization of anti-cancer activities of violacein: actions on tumor cells and the tumor microenvironment","volume":"12","author":"Dahlem","year":"2022","journal-title":"Front. Oncol."},{"key":"10.1016\/j.toxicon.2025.108501_bib10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.colsurfb.2017.09.027","article-title":"Interaction of violacein in models for cellular membranes: regulation of the interaction by the lipid composition at the air-water interface","volume":"160","author":"de Souza","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"10.1016\/j.toxicon.2025.108501_bib11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jcb.30295","article-title":"Violacein negatively modulates the colorectal cancer survival and epithelial-mesenchymal transition","volume":"123","author":"de Souza Oliveira","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.toxicon.2025.108501_bib12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.biotechadv.2016.06.003","article-title":"Advances in Chromobacterium violaceum and properties of violacein-Its main secondary metabolite: a review","volume":"34","author":"Dur\u00e1n","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"10.1016\/j.toxicon.2025.108501_bib13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11274-021-03120-4","article-title":"Multi-target drug with potential applications: violacein in the spotlight","volume":"37","author":"Dur\u00e1n","year":"2021","journal-title":"World J. Microbiol. Biotechnol."},{"key":"10.1016\/j.toxicon.2025.108501_bib14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1182\/blood-2004-02-0594","article-title":"Molecular mechanism of violacein-mediated human leukemia cell death","volume":"104","author":"Ferreira","year":"2004","journal-title":"Blood"},{"key":"10.1016\/j.toxicon.2025.108501_bib15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/sj.bjc.6603189","article-title":"Different susceptibility of osteosarcoma cell lines and primary cells to treatment with oncolytic adenovirus and doxorubicin or cisplatin","volume":"94","author":"Graat","year":"2006","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.toxicon.2025.108501_bib16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s13277-016-5265-x","article-title":"Violacein induces death of RAS-mutated metastatic melanoma by impairing autophagy process","volume":"37","author":"Gon\u00e7alves","year":"2016","journal-title":"Tumour Biol"},{"key":"10.1016\/j.toxicon.2025.108501_bib17","article-title":"Discerning perturbed assembly of lipids in a model membrane in presence of violacein: effects of membrane hydrophobicity","volume":"4","author":"Gupta","year":"2023","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"10.1016\/j.toxicon.2025.108501_bib18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ajodo.2004.07.025","article-title":"What do 8-bit and 12-bit grayscale mean and which should I use when scanning?","volume":"127","author":"Halazonetis","year":"2005","journal-title":"Am. J. Orthod. Dentofacial Orthop."},{"key":"10.1016\/j.toxicon.2025.108501_bib20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/PPO.0000000000000500","article-title":"Epidemiology of triple-negative breast cancer: a review","volume":"1","author":"Howard","year":"2021","journal-title":"Cancer J."},{"key":"10.1016\/j.toxicon.2025.108501_bib21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s44164-024-00066-3","article-title":"Biological characterization of breast cancer spheroid formed by fast fabrication method","volume":"1","author":"Iijima","year":"2024","journal-title":"In Vitro Model"},{"key":"10.1016\/j.toxicon.2025.108501_bib22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1200\/JCO.21.00278","article-title":"Revised neuroblastoma risk classification system: a report from the Children's Oncology group","volume":"39","author":"Irwin","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.toxicon.2025.108501_bib23","first-page":"7","article-title":"Is it time to start transitioning from 2D to 3D cell culture?","volume":"6","author":"Jensen","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.toxicon.2025.108501_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3816\/CBC.2009.n.005","article-title":"Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design","volume":"9","author":"Kassam","year":"2009","journal-title":"Clin. Breast Cancer"},{"key":"10.1016\/j.toxicon.2025.108501_bib25","article-title":"The natural pigment violacein potentially suppresses the proliferation and stemness of hepatocellular carcinoma cells in vitro","volume":"19","author":"Kim","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.toxicon.2025.108501_bib26","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/carcin\/bgi307","article-title":"Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in human colorectal cancer cells","volume":"3","author":"Kodach","year":"2006","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.toxicon.2025.108501_bib27","first-page":"381","article-title":"Advances in systemic therapies for triple negative breast cancer","volume":"30","author":"Leon-Ferre","year":"2023","journal-title":"BMJ"},{"key":"10.1016\/j.toxicon.2025.108501_bib28","article-title":"Assays on 3D tumor spheroids for exploring the light dosimetry of photodynamic effects under different gaseous conditions","volume":"6","author":"Li","year":"2024","journal-title":"J Biophotonics"},{"key":"10.1016\/j.toxicon.2025.108501_bib29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1290\/1071-2690(2000)036<0539:VCAIOA>2.0.CO;2","article-title":"Violacein cytotoxicity and induction of apoptosis in V79 cells","volume":"36","author":"Melo","year":"2000","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"10.1016\/j.toxicon.2025.108501_bib30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00432-023-04930-9","article-title":"Antitumor activity of natural pigment violacein against osteosarcoma and rhabdomyosarcoma cell lines","volume":"149","author":"Milosevic","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"10.1016\/j.toxicon.2025.108501_bib31","article-title":"Global, regional, and national epidemiology of childhood neuroblastoma (1990-2021): a statistical analysis of incidence, mortality, and DALYs","volume":"79","author":"Nong","year":"2024","journal-title":"eClinicalMedicine"},{"key":"10.1016\/j.toxicon.2025.108501_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2024.123184","article-title":"Multicellular tumor spheroids: a convenient in vitro model for translational cancer research","volume":"358","author":"Patel","year":"2024","journal-title":"Life Sci."},{"key":"10.1016\/j.toxicon.2025.108501_bib33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3390\/jcm13164765","article-title":"High-risk neuroblastoma challenges and opportunities for antibody-based cellular immunotherapy","volume":"13","author":"Persaud","year":"2024","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.toxicon.2025.108501_bib34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/cells12030360","article-title":"Comparison of radiation response between 2D and 3D cell culture models of different human cancer cell lines","volume":"12","author":"Raitanen","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.toxicon.2025.108501_bib35","first-page":"3","article-title":"Characterization of human neuroblastoma cell lines established before and after therapy","volume":"76","author":"Reynolds","year":"1986","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.toxicon.2025.108501_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.ymben.2013.08.004","article-title":"Systems metabolic engineering of Escherichia coli for production of the antitumor drugs violacein and deoxyviolacein","volume":"20","author":"Rodrigues","year":"2013","journal-title":"Metab. Eng."},{"key":"10.1016\/j.toxicon.2025.108501_bib37","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2217\/fon-2020-1021","article-title":"Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer","volume":"17","author":"Skinner","year":"2021","journal-title":"Future Oncol."},{"key":"10.1016\/j.toxicon.2025.108501_bib38","first-page":"2","article-title":"Mechanism and use of the commercially available viability stain","volume":"61","author":"Stocks","year":"2004","journal-title":"BacLight. Cytometry A"},{"key":"10.1016\/j.toxicon.2025.108501_bib39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41392-024-02121-7","article-title":"AXL signaling in cancer: from molecular insights to targeted therapies","volume":"1","author":"Yadav","year":"2025","journal-title":"Signal Transduct Target Ther"}],"container-title":["Toxicon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010125002764?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010125002764?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:56:36Z","timestamp":1772769396000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041010125002764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":38,"alternative-id":["S0041010125002764"],"URL":"https:\/\/doi.org\/10.1016\/j.toxicon.2025.108501","relation":{},"ISSN":["0041-0101"],"issn-type":[{"value":"0041-0101","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Antitumor activity of violacein in osteosarcoma, neuroblastoma and triple-negative breast cancer spheroids","name":"articletitle","label":"Article Title"},{"value":"Toxicon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxicon.2025.108501","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"108501"}}