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

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 in...

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Veröffentlicht in:European journal of medicinal chemistry 2018-10, Vol.158, p.743-752
Hauptverfasser: Ma, Long, Meng, Yuanyuan, Tu, Chunhao, Cao, Xiuqi, Wang, Haiyue, Li, Yuyin, Man, Shuli, Zhou, Jin, Li, Miao, Liu, Zhenxing, Su, Yanfang
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •HTF-1, a newly isolated cardiac glycoside from Helleborus thibetanus Franch., bears potent in vitro anti-cancer activity.•HTF-1 inhibits cancer cell in proliferation, migration and invasion; additionally, it causes S cell cycle arrest.•HTF-1 triggers caspase-9 dependent apoptosis pathway and double strand DNA breaks.•Mechanistically, HTF-1 activates JNK, but suppresses ERK and PI3K-Akt-mTOR pathways.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2018.09.019