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

作者：Ma, Long^*; Meng, Yuanyuan; Tu, Chunhao; Cao, Xiuqi; Wang, Haiyue; Li, Yuyin; Man, Shuli; Zhou, Jin; Li, Miao; Liu, Zhenxing; Su, Yanfang^*

来源：European Journal of Medicinal Chemistry, 2018, 158: 743-752.

DOI：10.1016/j.ejmech.2018.09.019

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

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 (DSB5). 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.

• 出版日期2018-10-5
• 单位天津科技大学; 天津大学