title: Ginsenoside F(2) induces apoptosis in humor gastric carcinoma cells through reactive oxygen species-mitochondria pathway and modulation of ASK-1/JNK signaling cascade in vitro and in vivo.
abstract: Ginsenoside F(2) (F(2)) is a potential bioactive metabolite of major ginsenosides. The potential anti-cancer effect of F(2) in gastric cancer cells has not been appraised. This study investigated the effects of F(2) on the production of reactive oxygen species (ROS). We also investigated the in vitro and in vivo effects of F(2) on the downstream signaling pathways leading to apoptosis in human gastric cancer cells. The in vitro data revealed that F(2) induces ROS accumulation followed by a decrease in mitochondrial transmembrane potential (MTP), and the release of cytochrome c (cyto c), which induced the caspase-dependent apoptosis. Further assay indicated that modulation of ASK-1/JNK pathway contributes to apoptosis. In vivo, F(2) exhibits the obvious anti-cancer effect compared with cisplatin with no obvious toxicity. Jointly, these results suggest that F(2) induces apoptosis by causing an accumulation of ROS and activating the ASK-1/JNK signaling pathway. This provides further support for the use of F(2) as a novel anticancer therapeutic candidate.
authors.affiliation: Department of Pharmaceutical Analysis & Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Jiangsu Center for New Drug Screening & National New Drug Screening Laboratory, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Ping-Hu
authors.initials: PH
authors.lastname: Zhang
authors.affiliation: State Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing, PR China. Electronic address: qwang49@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Analysis & Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China. Electronic address: songlinli64@126.com.
authors.forename: Song-Lin
authors.initials: SL
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D017382:Reactive Oxygen Species; C407883:ginsenoside F2; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human
keywords: ASK-1/JNK; Apoptosis; Ginsenoside F(2); Mitochondria; ROS; Subcutaneous tumor model