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Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum
Plant Biotechnology and Ethnobotany Laboratory, Faculty of Natural Sciences and Life, University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria
Metastasis Research Laboratory, GIGA-Cancer, University of Liege, Institute of Pathology B23 avenue de l'Hôpital 3, B-4000 Liege, Belgium
Pharmacognosy Laboratory, CIRM, University of Liege, Institute of Pharmacy B36 avenue de l'Hôpital 1, B-4000 Liege, Belgium
Marine Ecosystems and Aquacultural Laboratory, Faculty of Natural Sciences and Life, University of Bejaia, Targa Ouzemour, 06000 Bejaia, Algeria
* Author to whom correspondence should be addressed.
Received: 10 October 2013; in revised form: 18 November 2013 / Accepted: 20 November 2013 / Published: 2 December 2013
Abstract: 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 µM 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.
Keywords: Glaucium flavum; Papaveraceae; HPLC-DAD; protopine; bocconoline; anti-cancer
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Bournine, L.; Bensalem, S.; Wauters, J.-N.; Iguer-Ouada, M.; Maiza-Benabdesselam, F.; Bedjou, F.; Castronovo, V.; Bellahcène, A.; Tits, M.; Frédérich, M. Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum. Int. J. Mol. Sci. 2013, 14, 23533-23544.
Bournine L, Bensalem S, Wauters J-N, Iguer-Ouada M, Maiza-Benabdesselam F, Bedjou F, Castronovo V, Bellahcène A, Tits M, Frédérich M. Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum. International Journal of Molecular Sciences. 2013; 14(12):23533-23544.
Bournine, Lamine; Bensalem, Sihem; Wauters, Jean-Noël; Iguer-Ouada, Mokrane; Maiza-Benabdesselam, Fadila; Bedjou, Fatiha; Castronovo, Vincent; Bellahcène, Akeila; Tits, Monique; Frédérich, Michel. 2013. "Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum." Int. J. Mol. Sci. 14, no. 12: 23533-23544.