{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:38:08Z","timestamp":1789850288631,"version":"4.0.1"},"reference-count":22,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2013,12,2]],"date-time":"2013-12-02T00:00:00Z","timestamp":1385942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glaucium flavum is used in Algerian folk medicine to remove warts  (benign tumors). Its local appellations are Cheqiq el-asfar and Qarn el-djedyane. We have recently reported the anti-tumoral activity of Glaucium flavum root alkaloid extract against human cancer cells, in vitro and in vivo. The principal identified alkaloid in the extract was protopine. This study aims to determine which component(s) of Glaucium flavum root extract might possess potent antitumor activity on human cancer cells. Quantitative estimation of Glaucium flavum alkaloids was realized by HPLC-DAD. Glaucium flavum effect on human normal and cancer cell viability was determined using WST-1 assay. Quantification of alkaloids in Glaucium flavum revealed that the dried root part contained 0.84% of protopine and 0.07% of bocconoline (w\/w), while the dried aerial part contained only 0.08% of protopine, glaucine as the main alkaloid, and no bocconoline. In vitro evaluation of the growth inhibitory activity on breast cancer and normal cells demonstrated that purified protopine did not reproduce the full cytotoxic activity of the alkaloid root extract on cancer cell lines. On the other hand, bocconoline inhibited strongly the viability of cancer cells with an IC50 of 7.8 \u00b5M and only a low cytotoxic effect was observed against normal human cells. Our results showed for the first time that protopine is the major root alkaloid of Glaucium flavum. Finally, we are the first to demonstrate a specific anticancer effect of Glaucium flavum root extract against breast cancer cells, which can be attributed, at least in part, to bocconoline.<\/jats:p>","DOI":"10.3390\/ijms141223533","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T03:18:09Z","timestamp":1386040689000},"page":"23533-23544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum"],"prefix":"10.3390","volume":"14","author":[{"given":"Lamine","family":"Bournine","sequence":"first","affiliation":[{"name":"Plant Biotechnology and Ethnobotany Laboratory, Faculty of Natural Sciences and Life,  University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria"},{"name":"Metastasis Research Laboratory, GIGA-Cancer, University of Liege,  Institute of Pathology B23 avenue de l'H\u00f4pital 3, B-4000 Liege, Belgium"},{"name":"Pharmacognosy Laboratory, CIRM, University of Liege, Institute of Pharmacy B36 avenue de l'H\u00f4pital 1, B-4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihem","family":"Bensalem","sequence":"additional","affiliation":[{"name":"Plant Biotechnology and Ethnobotany Laboratory, Faculty of Natural Sciences and Life,  University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-No\u00ebl","family":"Wauters","sequence":"additional","affiliation":[{"name":"Pharmacognosy Laboratory, CIRM, University of Liege, Institute of Pharmacy B36 avenue de l'H\u00f4pital 1, B-4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mokrane","family":"Iguer-Ouada","sequence":"additional","affiliation":[{"name":"Marine Ecosystems and Aquacultural Laboratory, Faculty of Natural Sciences and Life,  University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadila","family":"Maiza-Benabdesselam","sequence":"additional","affiliation":[{"name":"Plant Biotechnology and Ethnobotany Laboratory, Faculty of Natural Sciences and Life,  University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha","family":"Bedjou","sequence":"additional","affiliation":[{"name":"Plant Biotechnology and Ethnobotany Laboratory, Faculty of Natural Sciences and Life,  University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Castronovo","sequence":"additional","affiliation":[{"name":"Metastasis Research Laboratory, GIGA-Cancer, University of Liege,  Institute of Pathology B23 avenue de l'H\u00f4pital 3, B-4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akeila","family":"Bellahc\u00e8ne","sequence":"additional","affiliation":[{"name":"Metastasis Research Laboratory, GIGA-Cancer, University of Liege,  Institute of Pathology B23 avenue de l'H\u00f4pital 3, B-4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Tits","sequence":"additional","affiliation":[{"name":"Pharmacognosy Laboratory, CIRM, University of Liege, Institute of Pharmacy B36 avenue de l'H\u00f4pital 1, B-4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Fr\u00e9d\u00e9rich","sequence":"additional","affiliation":[{"name":"Pharmacognosy Laboratory, CIRM, University of Liege, Institute of Pharmacy B36 avenue de l'H\u00f4pital 1, B-4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,12,2]]},"reference":[{"key":"ref_1","unstructured":"Qu\u00e9zel, P., and Santa, S. (1962). Nouvelle Flore D\u2019Alg\u00e9rie et des R\u00e9gions D\u00e9sertiques M\u00e9ridionales, Centre National de la Recherche Scientifique."},{"key":"ref_2","first-page":"77","article-title":"Yellow horned poppy: A new medicinal plant","volume":"10","author":"Schreter","year":"1976","journal-title":"Farmatsevticheskii Zhurnal"},{"key":"ref_3","unstructured":"Julve, P. Available online: http:\/\/www.tela-botanica.org\/bdtfx-nn-30228."},{"key":"ref_4","first-page":"64","article-title":"An ethnobotanical survey on hormozgan province, Iran","volume":"3","author":"Safa","year":"2013","journal-title":"Avicenna J. Phytomed"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0378-8741(03)00047-3","article-title":"Preliminary comparative analysis of medicinal plants used in the traditional medicine of Bulgaria and Italy","volume":"87","author":"Leporatti","year":"2003","journal-title":"J. Ethnopharmacol"},{"key":"ref_6","unstructured":"Baba-aissa, F. (2000). Encyclopedie des plante utiles: Flore d\u2019Alg\u00e9rie et du Maghreb, substances v\u00e9g\u00e9tales d\u2019Afrique d\u2019Orient et d\u2019Occident, \u00c9das, librairie moderne."},{"key":"ref_7","first-page":"502","article-title":"Anti-inflammatory, analgesic and antipyretic effects of glaucine in rats and mice","volume":"4","author":"Pinto","year":"1998","journal-title":"Pharm. Pharmacol. Commun"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/ptr.2650020411","article-title":"Glaucium flavum Crantz. Part v: Hypoglycemic activity of the aqueous extract","volume":"2","author":"Cabo","year":"2006","journal-title":"Phytother. Res"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.foodchem.2007.01.064","article-title":"Antioxidant activity and total phenolic content of selected Jordanian plant species","volume":"104","author":"Tawaha","year":"2007","journal-title":"Food Chem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.phymed.2013.06.007","article-title":"Revealing the anti-tumoral effect of Algerian Glaucium flavum roots against human cancer cells","volume":"20","author":"Bournine","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00570773","article-title":"Glaucium alkaloids","volume":"15","author":"Israilov","year":"1979","journal-title":"Chem. Nat. Comp"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/0031-9422(88)84134-7","article-title":"Minor alkaloids of Glaucium flavum","volume":"27","author":"Daskalova","year":"1988","journal-title":"Phytochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1023\/B:PHAC.0000048907.58847.c6","article-title":"HPLC determination of glaucine in yellow horn poppy grass (Glaucium flavum Crantz.)","volume":"38","author":"Lapa","year":"2004","journal-title":"Pharm. Chem. J"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1135\/cccc19743352","article-title":"Further alkaloids from Glaucium flavum CR","volume":"39","year":"1974","journal-title":"Collect. Czech. Chem. Commun"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1080\/14786410902904418","article-title":"Alkaloids from Glaucium flavum from Sardinia","volume":"24","author":"Petitto","year":"2010","journal-title":"Nat. Prod. Res"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2011.09.042","article-title":"Protopine, a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines","volume":"315","author":"Chen","year":"2012","journal-title":"Cancer Lett"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejphar.2008.06.045","article-title":"Protective effects of protopine on hydrogen peroxide-induced oxidative injury of PC12 cells via Ca2+ antagonism and antioxidant mechanisms","volume":"591","author":"Xiao","year":"2008","journal-title":"Eur. J. Pharmacol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.sajb.2006.03.014","article-title":"Benzo[c]phenanthridine alkaloids from stem bark of the Forest Knobwood, Zanthoxylum davyi (Rutaceae)","volume":"72","author":"Tarus","year":"2006","journal-title":"S. Afr. J. Bot"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1055\/s-2007-969890","article-title":"Further alkaloids from bark of Fagara mayu","volume":"48","author":"Assem","year":"1983","journal-title":"Planta Medica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.bse.2003.08.012","article-title":"Phytochemical variations within populations of Platycapnos saxicola Willk","volume":"32","author":"Suau","year":"2004","journal-title":"Biochem. Syst. Ecol"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1172\/JCI107470","article-title":"Culture of Human endothelial cells derived from umbilical veins identification by morphologic and immunologic criteria","volume":"52","author":"Jaffe","year":"1973","journal-title":"J. Clin. Investig"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1182\/blood-2010-08-298810","article-title":"Dentin matrix protein 1 induces membrane expression of VE-cadherin on endothelial cells and inhibits VEGF-induced angiogenesis by blocking VEGFR-2 phosphorylation","volume":"117","author":"Pirotte","year":"2011","journal-title":"Blood"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/12\/23533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:51:01Z","timestamp":1760219461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/12\/23533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,2]]},"references-count":22,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2013,12]]}},"alternative-id":["ijms141223533"],"URL":"https:\/\/doi.org\/10.3390\/ijms141223533","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,2]]}}}