Department of Orthopaedics, Minzu Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, People's Republic of China.
Department of Hepatic Diseases, Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang, People's Republic of China.
Cell Biol Int. 2023 Aug;47(8):1344-1353. doi: 10.1002/cbin.12021. Epub 2023 Mar 29.
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 Ca /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.
蟾毒灵是中药蟾酥中的主要强心化合物，已被用于癌症治疗多年。然而，蟾毒灵诱导骨肉瘤（OS）自噬的分子机制尚不完全清楚。在本研究中，表明蟾毒灵诱导凋亡和自噬之间的串扰，导致 OS 细胞死亡。在机制上，蟾毒灵通过增加微管相关蛋白 1A/1B-轻链 3（LC3）-II/LC3-I 的比值，诱导自噬，并通过 caspase 依赖性途径诱导凋亡。自噬的抑制促进了蟾毒灵诱导的细胞死亡。相反，凋亡的抑制增强了蟾毒灵诱导的自噬。此外，研究发现蟾毒灵激活了钙/钙调蛋白依赖性蛋白激酶β/AMPK/Beclin1 通路，导致自噬的诱导。这些发现为蟾毒灵在 OS 细胞中介导自噬和凋亡的机制提供了深入了解。
