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

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 ± 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.