@article {145386,
	title = {Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells.},
	journal = {Journal of natural products},
	volume = {80},
	year = {2017},
	month = {2017 Dec 22},
	pages = {3203-3210},
	abstract = {<p>We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC50 of 68 {\textpm} 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity against cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G2/M regulators cyclin B1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential anticancer lead.</p>
},
	issn = {1520-6025},
	doi = {10.1021/acs.jnatprod.7b00546},
	author = {El Gaafary, Menna and Shahira M. Ezzat and Abeer M. Elsayed and Sabry, Omar M and Hafner, Susanne and Lang, Sophia and Schmiech, Michael and Syrovets, Tatiana and Simmet, Thomas}
}
