2. Academic Validation
  3. 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

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.
Long Ma 1,  Yuanyuan Meng 2,  Chunhao Tu 2,  Xiuqi Cao 2,  Haiyue Wang 2,  Yuyin Li 3,  Shuli Man 3,  Jin Zhou 2,  Miao Li 2,  Zhenxing Liu 3,  Yanfang Su 4
Affiliations

Affiliations

  • 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: malong@tust.edu.cn.
  • 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: suyanfang@tju.edu.cn.
PMID: 30245398 DOI: 10.1016/j.ejmech.2018.09.019
Abstract

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.

Keywords

Anti-Cancer; Apoptosis; Cardiac glycoside; ERK and JNK pathways; Helleborus thibetanus Franch.; PI3K-Akt-mTOR pathway.

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