Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells

Abstract

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.

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October University for Modern Sciences and Arts, جامعة أكتوبر للعلوم الحديثة والآداب, University of Modern Sciences and Arts, MSA University, acovenoside a, cardenolide, caspase 3, cyclin B1, cyclin dependent kinase 1, cytotoxic agent, doxorubicin, ebselen, norphenazone, protein p53, reactive oxygen metabolite, tempol, unclassified drug, acovenoside A, antineoplastic agent, cardenolide, doxorubicin, reactive oxygen metabolite, Acokanthera oppositifolia, apoptosis, Article, cell cycle, cell cycle progression, cell proliferation, cell viability, controlled study, cytokinesis, cytotoxicity, DNA fragmentation, drug mechanism, drug sensitivity, fluorescence, G2 phase cell cycle checkpoint, human, human cell, IC50, lung fibroblast, lung non-small cell carcinoma cell line, M phase cell cycle checkpoint, mitochondrial membrane potential, mitosis, mitosis inhibition, non small cell lung cancer, oxidative stress, pericarp, peripheral blood mononuclear cell, protein phosphorylation, shrub, A-549 cell line, apoptosis, cell survival, drug effect, epidemiology, fibroblast, lung tumor, metabolism, mitochondrial membrane, mitosis, mononuclear cell, non small cell lung cancer, tumor cell line, A549 Cells, Antineoplastic Agents, Apoptosis, Carcinoma, Non-Small-Cell Lung, Cardenolides, Cell Line, Tumor, Cell Proliferation, Cell Survival, DNA Fragmentation, Doxorubicin, Epidemiologic Studies, Fibroblasts, G2 Phase Cell Cycle Checkpoints, Humans, Leukocytes, Mononuclear, Lung Neoplasms, Mitochondrial Membranes, Mitosis, Reactive Oxygen Species

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