Mechanisms underlying the anti-tumoral effect of Allium roseum L. extract on Chronic Myeloid Leukemia K562 cells

Communication de Soumaya Souid, doctorante à l”IPT, Colloque Jeunes Chercheurs de l’IPT (8-9 décembre 2016)

Background and objectives: Among various strategies that have been explored to overcome tumor drug
resistance, the combination of current chemotherapy with plant extracts as chemosensitizers has emerged
as a promising one. In the present study, we investigated for the first time the anti-cancer activity of Allium
roseum L. extract, a wild edible species in North Africa and its mechanisms against the well-characterized
human Chronic Myelogenous Leukemia (CML) K562 cells in vitro.
Methodology: K562 cells were treated with dehydrated aqueous (DAE) and fresh extracts in a time- and
dose-dependent manner. Cell viability and cytotoxicity were evaluated by MTT and LDH assays. Cell cycle
analysis and the apoptosis levels were assessed by flow cytometry. Using Western blot and Elisa assays, we
elicited key signaling pathways and effectors proteins targeted by DAE.
Results: DAE exhibited the highest antiproliferative activity on K562 cells even compared with the
chemotherapeutic drug Imatinib Mesylate, a tyrosine kinase inhibitor that targets the fusion oncoprotein
BCR-ABL responsible for this disease. DAE disturbed the cell cycle progression and induced the apoptosis
of K562 cells. Chemical analysis of DAE showed a diversity of organosulfur compounds RCSO and high
amount of allicin, suggesting that such molecule may be behind the anti-cancer effect of Allium roseum
extract. Similarly to Imatinib Mesylate, DAE inhibitory effect was associated with the dephosphorylation
of BCR-ABL kinase and interfered with the major prosurvival pathways, ERK1/2 and Akt. 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 pro-apoptotic effectors, Bim and Bax, and cell cycle
inhibitor p27. Finally, we found that DAE-treated K562 cells presented a reduced secretion of the proangiogenic
effector, Vascular Endothelial Growth Factor ( VEGF), compared to the non-treated cells.
Conclusion: Our data suggest that Allium roseum L. extract has great potential as a non-toxic cheap and
effective alternative to conventional chemotherapy that presents a dual inhibitory effect on both cancer
cell viability, through FOXO3 activation, and its angiogenic promoting regulator VEGF.