A cardiac glycoside HTF-1 isolated from Helleborus thibetanus Franch displays potent in vitro anti-cancer activity via caspase-9, MAPK and PI3K-Akt-mTOR pathways
- Eur J Med Chem. 2018 Oct 5:158:743-752. doi: 10.1016/j.ejmech.2018.09.019.
- 1. Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, School of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: [email protected].
- 2. Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, School of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
- 3. Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, School of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin 300457, China.
- 4. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: [email protected].
Experiments have been undertaken and for the first time, we have identified that a new cardiac glycoside (CG) isolated from Helleborus thibetanus Franch. a plant endemic to China, bears potent anti-cancer activity. We have named it as HTF-1. By using in vitro cell models, we have found that HTF-1 induces Apoptosis against several types of Cancer cells in a concentration- and time-dependent manner. It is able to inhibit Cancer cell in proliferation, migration and invasion. HTF-1 causes S cell cycle arrest. Further-on, we have identified that HTF-1 triggers caspase-9 dependent Apoptosis pathway and double strand DNA breaks (DSBs). Additionally, HTF-1 activates JNK, but suppresses ERK and PI3K-Akt-mTOR pathways. Collectively, the above-mentioned mechanisms contribute to the anti-cancer activity of HTF-1. It is rare to discover novel anti-cancer CG during the past couple of decades. We believe that our work will enrich the understanding of CGs; also, pave the way for natural product-based anti-cancer drug development.