禾本科植物产物蟾酥毒素是传统中医药材蟾酥的主要心脏强心化合物。多年来，蟾酥毒素已被用于癌症治疗。然而，蟾酥毒素诱导的骨肉瘤（OS）自噬的分子机制尚不完全了解。本研究表明，蟾酥毒素诱导凋亡和自噬之间的相互作用，导致OS细胞死亡。机制上，蟾酥毒素通过增加微管相关蛋白1A/1B-轻链3（LC3）-II/LC3-I比率诱导自噬，通过半胱氨酸依赖性途径诱导凋亡。抑制自噬促进蟾酥毒素诱导的细胞死亡，而抑制凋亡则增强蟾酥毒素诱导的自噬。此外，发现蟾酥毒素通过激活Ca2+ /钙调蛋白依赖性蛋白激酶β/AMPK/Beclin1通路诱导自噬。这些发现为了解蟾酥毒素在OS细胞中介导自噬和凋亡的机制提供了一种机械性理解。© 2023 International Federation for Cell Biology。

Bufalin, a major cardiotonic compound of the traditional Chinese medicine Chanshu has been used for cancer treatment for several years. However, the molecular mechanisms of Bufalin-induced autophagy in osteosarcoma (OS) is not fully understood. In the present study, it was shown that Bufalin induced crosstalk between apoptosis and autophagy, which resulted in OS cell death. Mechanistically, Bufalin induced autophagy by increased the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I, and inducing apoptosis via the caspase-dependent pathway. Inhibition of autophagy promoted Bufalin-induced cell death. In contrast, suppression of apoptosis enhanced Bufalin-induced autophagy. In addition, it was found that Bufalin activated the Ca2+ /calmodulin-dependent protein kinase β/AMPK/Beclin1 pathway, which resulted in induction of autophagy. These findings provide a mechanistic understanding of the means by which Bufalin mediates autophagy and apoptosis in OS cells.© 2023 International Federation for Cell Biology.