2-Deoxy-Rh2: A novel ginsenoside derivative, as dual-targeting anti-cancer agent via regulating apoptosis and glycolysis
Publication date: April 2020Source: Biomedicine & Pharmacotherapy, Volume 124Author(s): Huan Gao, Di Liang, Chenchen Li, Guoxing Xu, Mengnan Jiang, Heng Li, Jianyuan Yin, Yanqing SongAbstract20(S)-Rh2 is a ginsenoside isolated from Panax ginseng, which exhibits anti-cancer activities on various human cancer cells. A novel 20(S)-Rh2 derivative, 2-Deoxy-Rh2 was synthesized and hybridized with protopanaxadiol and 2-deoxy-glucose in an attempt to enhance the anticancer activity. Through screening the antitumor effect against various cell lines by MTT assay, 2-Deoxy-Rh2 especially resulted in a concentration-dependent and time-dependent inhibition of viability in MCF-7 human breast cancer cells. Multiple methods were used to explore the cellular and molecular mechanisms of 2-Deoxy-Rh2 as a potent anti-cancer agent. In MCF-7 cells, 2-Deoxy-Rh2 triggered apoptosis, stimulated ROS production and disrupted normal mitochondrial membrane potential. Meantime, 2-Deoxy-Rh2 eff ;ectively suppressed the glucose uptake capabilities and intracellular ATP production. The cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were significantly decreased in response to 2-Deoxy-Rh2, which were carried out to assess the overall glycolytic flux and mitochondrial respiration. Docking studies and molecular dynamics simulations were performed to verify the binding mode of 2-DG and 2-Deoxy-Rh2 with hexokinase II, with results showing that 2-Deoxy-Rh2 could easily fit into t...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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