Browsing by Author "Lang S."

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    Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells
    (American Chemical Society, 2017) El Gaafary M.; Ezzat, Shahira M; El Sayed A.M.; Sabry O.M.; Hafner S.; Lang S.; Schmiech M.; Syrovets T.; Simmet T.; Department of Pharmacognosy; College of Pharmacy; Cairo University; Giza; 11562; Egypt; Pharmacognosy Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; 11562; Egypt; Institute of Pharmacology of Natural Products and Clinical Pharmacology; Ulm University; Ulm; D-89081; Germany
    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 IC 50 of 68 � 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 G 2 /M regulators cyclin B 1 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. � 2017 The American Chemical Society and American Society of Pharmacognosy.