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.

中文翻译：

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Acovenoside A在非小细胞肺癌细胞中诱导有丝分裂灾难并随后凋亡。

我们调查了心果内酯糖苷Acovenoside A对非小细胞肺癌细胞的细胞毒性潜力。肺癌是与癌症相关的死亡率的主要原因，也是第二大最常见的癌症。流行病学研究表明，常规服用强心苷与各种癌症的发生率较低之间存在直接的相关性。从Acokanthera oppositifolia的果皮中分离出的Acovenoside A通过IC _50可以有效抑制A549非小细胞肺癌细胞的增殖并诱导其细胞毒性暴露48小时后的平均值为68±3 nM。与抗肿瘤药阿霉素相比，蛇毒苷A在抑制A549癌细胞活力方面更有效。此外，椰油甙A对癌细胞具有选择性，对肺成纤维细胞的毒性明显较小，而对外周血单核细胞则无毒性。对Acovenoside A处理的A549细胞的细胞周期概况分析显示，由于G ₂ / M调节剂cyclin B _1的积累，导致有丝分裂停滞CDK1和胞质分裂失败。此外，椰油甙A影响线粒体膜的完整性并诱导自由基氧的产生，从而导致经典凋亡的诱导，这由caspase 3活化和DNA片段化表现出来。根据我们的研究结果，蛇床皂苷A作为潜在的抗癌药物值得进一步研究。