{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:43:16Z","timestamp":1762324996760,"version":"3.37.3"},"reference-count":46,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"crossref","award":["CDS - APQ-02540-15"],"award-info":[{"award-number":["CDS - APQ-02540-15"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["431330\/2018-2"],"award-info":[{"award-number":["431330\/2018-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["GD - 42313\/2015-7"],"award-info":[{"award-number":["GD - 42313\/2015-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50\u2009=\u20092.1\u2009\u00b5g\/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS\/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate\/propidium iodide (V-FITC\/PI) staining showed\n\t\t\t\t\tFAv_5 to promote cell cycle arrest at the G0\/G1-phase as well as apoptotic cell death. Overall, these findings highlight A.\u00a0velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A.\u00a0velutina and species conservation strategies have also been highlighted.<\/jats:p>","DOI":"10.1055\/a-1395-9046","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T23:27:35Z","timestamp":1618442855000},"page":"429-439","source":"Crossref","is-referenced-by-count":6,"title":["A Withanolide-rich Fraction of Athenaea velutina Induces Apoptosis and Cell Cycle Arrest in Melanoma B16F10 Cells"],"prefix":"10.1055","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-0328","authenticated-orcid":false,"given":"Alisson A.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziela D. A.","family":"Lima","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Geral, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Minas Gerais, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marin\u00eas","family":"Eiterer","sequence":"additional","affiliation":[{"name":"Independent Researcher"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"La\u00eds A.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana A.","family":"A. do Vale","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Geral, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Minas Gerais, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0199-4521","authenticated-orcid":false,"given":"Ana C.","family":"Zanatta","sequence":"additional","affiliation":[{"name":"Universidade Estadual Paulista (Unesp), Instituto de Qu\u00edmica, Araraquara, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo C.","family":"Bressan","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro L.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Geral, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Minas Gerais, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o P. V.","family":"Leite","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Vi\u00e7osa, Vi\u00e7osa, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biotechadv.2019.01.004","article-title":"Current status and contemporary approaches to the discovery of antitumor agents from higher plants","volume":"38","author":"G Agarwal","year":"2020","journal-title":"Biotechnol Adv"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"A L Harvey","year":"2015","journal-title":"Nat Rev Drug Discov"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.fct.2014.11.004","article-title":"The use of plant-derived bioactive compounds to target cancer stem cells and modulate tumor microenvironment","volume":"75","author":"F Pistollato","year":"2015","journal-title":"Food Chem Toxicol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.biotechadv.2015.08.001","article-title":"Discovery and resupply of pharmacologically active plant-derived natural products: a review","volume":"33","author":"A G Atanasov","year":"2015","journal-title":"Biotechnol Adv"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/iep.12351","article-title":"Screening of plants from the Brazilian Atlantic Forest let to identification of Athenaea velutina (Solanaceae) as a novel source of antimetastatic agents","volume":"101","author":"A A Almeida","year":"2020","journal-title":"Int J Exp Pathol"},{"key":"ref6","first-page":"1","article-title":"Antibacterial screening of plants from the Brazilian Atlantic Forest led to the identification of active compounds in Miconia latecrenata (DC.) Naudin","volume":"34","author":"L A Rodrigues","year":"2020","journal-title":"Nat Prod Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1002\/hlca.201000126","article-title":"Withanolides from Aureliana fasciculata var. fasciculata","volume":"93","author":"R C Almeida-Lafet\u00e1","year":"2010","journal-title":"Helv Chim Acta"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.3390\/molecules23123160","article-title":"Leishmanicidal activity of withanolides from Aureliana fasciculata var. fasciculata","volume":"23","author":"S CM Lima","year":"2018","journal-title":"Molecules"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e1700455","DOI":"10.1002\/cbdv.201700455","article-title":"Athenolide A, a new steroidal lactone from the leaves of Athenaea martiana (Solanaceae) determined by means of HPLC-HR-MS-SPE-NMR analysis","volume":"15","author":"E L Silva","year":"2018","journal-title":"Chem Biodivers"},{"key":"ref10","first-page":"127","volume-title":"Withanolides and related Steroids","author":"R I Misico","year":"2011"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.4103\/0973-8258.74130","article-title":"Withanolides: phytoconstituents with significant pharmacological activities","volume":"4","author":"A Singh","year":"2010","journal-title":"Int J Green Pharm"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5805","DOI":"10.1021\/ja00952a061","article-title":"The isolation and structural elucidation of a novel steroidal tumor inhibitor from Acnistus arborescens","volume":"87","author":"S M Kupchan","year":"1965","journal-title":"J Am Chem Soc"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"7517","DOI":"10.1039\/jr9650007517","article-title":"Constituents of Withania somnifera Dun. Part. IV. The structure of Withaferin A","author":"D Lavie","year":"1965","journal-title":"J Chem Soc"},{"key":"ref14","first-page":"1","article-title":"Withaferin A: from ayurvedic folk medicine to preclinical anti-cancer drug","volume":"171","author":"B Hassannia","year":"2020","journal-title":"Biochem Pharmacol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3390\/molecules21081013","article-title":"Cytotoxicity, post-treatment recovery, and selectivity analysis of naturally occurring podophyllotoxins from Bursera fagaroides var. fagaroides on breast cancer cell lines","volume":"21","author":"O A Pe\u00f1a-Mor\u00e1n","year":"2016","journal-title":"Molecules"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e1600280","DOI":"10.1002\/cbdv.201600280","article-title":"Metabolite profiling in Withania somnifera roots hydroalcoholic extract using LC\/MS, GC\/MS, and NMR spectroscopy","volume":"14","author":"M K Trivedi","year":"2017","journal-title":"Chem Biodivers"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/rcm.4835","article-title":"Analysis and development of structure-fragmentation relationships in withanolides using an electrospray ionization quadrupole time-of-flight tandem mass spectrometry hybrid instrument","volume":"25","author":"S G Musharraf","year":"2011","journal-title":"Rapid Commun Mass Spectrom"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bse.2013.12.026","article-title":"Chemotaxonomic characterization and chemical similarity of tribes\/genera of the Solanoideae subfamily (Solanaceae) based on occurrence of withanolides","volume":"54","author":"A GS Pigatto","year":"2014","journal-title":"Biochem Syst Ecol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1124\/dmd.109.028373","article-title":"Detection and characterization of a new metabolite of 17\u03b1-methyltestosterone","volume":"37","author":"\u00d3 J Pozo","year":"2009","journal-title":"Drug Metab Dispos"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1002\/tax.12089","article-title":"The nomenclatural re-establishment of Athenaea Sendtn. (Solanaceae) with a nomenclatural synopsis of the genus","volume":"68","author":"I MC Rodrigues","year":"2019","journal-title":"Taxon"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ejphar.2013.06.009","article-title":"Molecular approaches towards development of purified natural products and their structurally known derivatives as efficient anti-cancer drugs: current trends","volume":"714","author":"S K Saha","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41568-018-0038-z","article-title":"Every step of the way: integrins in cancer progression and metastasis","volume":"18","author":"H Hamidi","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12248-013-9531-1","article-title":"Molecular targets and mechanisms of cancer prevention and treatment by Withaferin A, a naturally occurring steroidal lactone","volume":"16","author":"A R Vyas","year":"2013","journal-title":"AAPS J"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"S Elmore","year":"2007","journal-title":"Toxicol Pathol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ejmech.2017.09.004","article-title":"Structure-based design, synthesis, and biological evaluation of withaferin A-analogues as potent apoptotic inducers","volume":"140","author":"G G Llanos","year":"2017","journal-title":"Eur J Med Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"IL34","DOI":"10.1055\/s-0033-1348513","article-title":"The search for antiproliferative withanolides from solanaceous species of the US","volume":"79","author":"B N Timmermann","year":"2013","journal-title":"Planta Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/1476-4598-9-239","article-title":"Withanolide D induces apoptosis in leukemia by targeting the activation of neutral sphingomyelinase-ceramide cascade mediated by synergistic activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase","volume":"9","author":"S Mondal","year":"2010","journal-title":"Mol Cancer"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1021\/np100112p","article-title":"Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma","volume":"73","author":"A K Samadi","year":"2010","journal-title":"J Nat Prod"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"PD104","DOI":"10.1055\/s-0032-1320472","article-title":"Withaferin A activity against glioblastoma cells: supression of microtubule dynamics","volume":"78","author":"D D Rocha","year":"2012","journal-title":"Planta Med"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/sj.neo.7900101","article-title":"Cell cycle and apoptosis","volume":"2","author":"B Pucci","year":"2000","journal-title":"Neoplasia"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10555-008-9173-4","article-title":"Mechanics, malignancy, and metastasis: the force journey of a tumor cell","volume":"28","author":"S Kumar","year":"2009","journal-title":"Cancer Metastasis Rev"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.apsb.2015.07.005","article-title":"Cancer metastases: challenges and opportunities","volume":"5","author":"X Guan","year":"2015","journal-title":"Acta Pharm Sin B"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tiv.2018.07.015","article-title":"Synthesis and antimetastatic activity evaluation of cinnamic acid derivatives containing 1,2,3-triazolic portions","volume":"53","author":"G DA Lima","year":"2018","journal-title":"Toxicol In Vitro"},{"key":"ref34","first-page":"95","article-title":"Estudios sobre Solanaceae XXX. Revision de Aureliana","volume":"30","author":"A T Hunziker","year":"1990","journal-title":"Darwiniana"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1590\/2175-78602001528003","article-title":"Diversidade taxon\u00f4mica e distribui\u00e7\u00e3o geogr\u00e1fica das solan\u00e1ceas que ocorrem no Sudeste Brasileiro (Acnistus, Athenaea, Aureliana, Brunfelsia e Cyphomandra)","volume":"52","author":"L AF Carvalho","year":"2001","journal-title":"Rodriguesia"},{"key":"ref36","first-page":"1","volume-title":"Coordena\u00e7\u00e3o de Recursos Naturais e Estudos Ambientais. Biomas e sistema costeiro-marinho do Brasil: compat\u00edvel com a escala 1\u2009:\u2009250\u2009000","author":"IBGE","year":"2019","edition":"1st ed."},{"key":"ref38","first-page":"1","volume-title":"\u00c1rvores da Mata Atl\u00e2ntica: livro ilustrado para identifica\u00e7\u00e3o de esp\u00e9cies t\u00edpicas de Floresta Estacional Semidecidual","author":"M VRC Sim\u00e3o","year":"2017","edition":"1st ed."},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6750-5-12","article-title":"A simple technique for quantifying apoptosis in 96-well plates","volume":"5","author":"D Ribble","year":"2005","journal-title":"BMC Biotechnol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1182\/blood.V84.5.1415.bloodjournal8451415","article-title":"Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis","volume":"84","author":"G Koopman","year":"1994","journal-title":"Blood"},{"key":"ref41","first-page":"301","article-title":"Analysis of cell cycle by flow cytometry","volume":"281","author":"P Pozarowski","year":"2004","journal-title":"Methods Mol Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1021\/np100201p","article-title":"Antifungal and cytotoxic activity of withanolides from Acnistus arborescens","volume":"73","author":"V Roumy","year":"2010","journal-title":"J Nat Prod"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.phytochem.2016.07.003","article-title":"Withanolides from leaves of cultivated Acnistus arborescens","volume":"130","author":"P H Batista","year":"2016","journal-title":"Phytochemistry"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.phytochem.2007.10.024","article-title":"Withanolides from Withania somnifera roots","volume":"69","author":"L Misra","year":"2008","journal-title":"Phytochemistry"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.fitote.2009.05.011","article-title":"Cytotoxicity of withanolides isolated from Acnistus arborescens","volume":"80","author":"C P Cordero","year":"2009","journal-title":"Fitoterapia"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1021\/np200635r","article-title":"Cytotoxic withanolide constituents of Physalis longifolia","volume":"74","author":"H Zhang","year":"2011","journal-title":"J Nat Prod"},{"volume-title":"Estudo fitoqu\u00edmico e da atividade antimelanoma de Aureliana velutina Sendtn. (Solanaceae) [Thesis]","year":"2019","author":"A A Almeida","key":"ref47"}],"container-title":["Planta Medica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1395-9046.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:50:32Z","timestamp":1651798232000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1395-9046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,14]]},"references-count":46,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2022,5,5]]},"published-print":{"date-parts":[[2022,5]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1395-9046","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0032-0943","1439-0221"],"issn-type":[{"type":"print","value":"0032-0943"},{"type":"electronic","value":"1439-0221"}],"subject":[],"published":{"date-parts":[[2021,4,14]]}}}