Three bufadienolides induce cell death in the human lung cancer cell line CL1-5 mainly through autophagy
- Bioorg Med Chem Lett. 2021 Jan 1:31:127715. doi: 10.1016/j.bmcl.2020.127715.
- 1. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan.
- 2. Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National ChungHsing University, 145 Xingda Rd., South Dist., Taichung 402, Taiwan.
The effects of 3 bufadienolides, namely kalantuboside B, kalantuboside A, and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung Cancer cells. In contrast to their apoptosis-promoting activity in other Cancer cells, these bufadienolides only slight or did not induce Apoptosis in CL1-5 Cancer cells. Instead, they activated an Autophagy pathway, as indicated by increased autophagosome formation. Autophagy induced by these bufadienolides was demonstrated to be linked to the down-regulation of p-mTOR and the up-regulation of LC3-II, ATG5, Atg7, and Beclin-1. Our findings revealed an Autophagy as the alternative mechanism of drug action by bufadienolides in CL1-5 lung Cancer cells and provided evidence that bufadienolides are a potential therapeutic strategy for highly metastatic human lung Cancer.