title: Allium Roseum L. Extract Exerts Potent Suppressive Activities on Chronic Myeloid Leukemia K562 Cell Viability Through the Inhibition of BCR-ABL, PI3K/Akt, and ERK1/2Pathways and the Abrogation of VEGF Secretion.
abstract: Use of plant extracts, alone or combined to the current chemotherapy as chemosensitizers, has emerged as a promising strategy to overcome tumor drug resistance. Here, we investigated the anticancer activity of Allium roseum L. extracts, a wild edible species in North Africa, on human Chronic Myeloid Leukemia (CML) K562 cells. The dehydrated aqueous extract (DAE) disturbed the cell cycle progression and induced the apoptosis of K562 cells. Chemical analysis of DAE showed a diversity of organosulfur compounds S-alk(en)yl-cysteine sulfoxides (RCSO) and high amount of allicin, suggesting that such molecule may be behind its antitumor effect. DAE was efficient in inhibiting K562 cell viability. DAE inhibitory effect was associated with the dephosphorylation of the BCR-ABL kinase and interfered with ERK1/2, Akt, and STAT5 pathways. Furthermore, we found that DAE-induced inactivation of Akt kinase led to the activation of its target FOXO3 transcription factor, enhancing the expression of FOXO3-regulated proapoptotic effectors, Bim and Bax, and cell cycle inhibitor p27. Finally, we found that DAE reduced the secretion of vascular endothelial growth factor. Overall, our data suggest that A. roseum extract has great potential as a nontoxic cheap and effective alternative to conventional chemotherapy.
authors.affiliation: a Institut Pasteur de Tunis, LR11IPT04 Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses , Tunis , Tunisie.|b Université de Tunis El Manar , Tunis , Tunisie.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Souid
authors.affiliation: c Laboratoire d'Ecologie Pastorale , Institut des régions Arides de Médenine , Tunisie.
authors.forename: Hanen
authors.initials: H
authors.lastname: Najjaa
authors.affiliation: a Institut Pasteur de Tunis, LR11IPT04 Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses , Tunis , Tunisie.|b Université de Tunis El Manar , Tunis , Tunisie.
authors.forename: Ichrak
authors.initials: I
authors.lastname: Riahi-Chebbi
authors.affiliation: b Université de Tunis El Manar , Tunis , Tunisie.|d Institut Pasteur de Tunis, LTCII LR11IPT02 , Tunis , Tunisie.
authors.forename: Meriam
authors.initials: M
authors.lastname: Haoues
authors.affiliation: c Laboratoire d'Ecologie Pastorale , Institut des régions Arides de Médenine , Tunisie.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Neffati
authors.affiliation: e CETU Innophyt , Université François Rabelais, avenue Monge , France, Tours.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arnault
authors.affiliation: f IRBI, UMR CNRS 6035 , Université François Rabelais, avenue Monge , France, Tours.
authors.forename: Jacques
authors.initials: J
authors.lastname: Auger
authors.affiliation: a Institut Pasteur de Tunis, LR11IPT04 Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses , Tunis , Tunisie.|b Université de Tunis El Manar , Tunis , Tunisie.
authors.forename: Habib
authors.initials: H
authors.lastname: Karoui
authors.affiliation: b Université de Tunis El Manar , Tunis , Tunisie.|d Institut Pasteur de Tunis, LTCII LR11IPT02 , Tunis , Tunisie.
authors.forename: Makram
authors.initials: M
authors.lastname: Essafi
authors.affiliation: a Institut Pasteur de Tunis, LR11IPT04 Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses , Tunis , Tunisie.|b Université de Tunis El Manar , Tunis , Tunisie.
authors.forename: Khadija
authors.initials: K
authors.lastname: Essafi-Benkhadir
mesh_terms: D000490:Allium / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D010936:Plant Extracts; D050799:STAT5 Transcription Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D016044:Fusion Proteins, bcr-abl; D051057:Proto-Oncogene Proteins c-akt