title: Autophagy antagonizes apoptosis induced by flavan enantiomers from Daphne giraldii in hepatic carcinoma cells in vitro.
abstract: Enantiomers account for quite a large percentage of compounds in natural products. Our team is interested in the separation and biological activity of racemic compounds. In this report, four pairs of prenylated flavan enantiomers [(±)-1-(±)-4], including five new compounds, were isolated from the stem and root bark of Daphne giraldii, and separated successfully by using chiral chromatographic column. Their planar structures and absolute configurations were established by comprehensive spectroscopic analyses as well as circular dichroism (CD) spectroscopy. The isolates had a selective cytotoxicity towards hepatic carcinoma cell lines. Among them, new compound (+)-4 showed a more potent inhibitory effect on Hep3B cells with an IC50value of 30.3 μM, compared with its racemic mixture 4. Therefore, the action mechanism of (+)-4in vitro was subsequently investigated. The morphological observation and Western blot analysis demonstrated that (+)-4 could markedly induce apoptosis through intrinsic and extrinsic pathways, and also cause autophagy by increasing the phosphorylation of AMP-activated protein kinase (AMPK) in Hep3B cells. After treatment with the autophagic inhibitor bafilomycin A1 (Baf A1), (+)-4-induced apoptosis increased significantly, suggesting that the autophagy induced by (+)-4 performed a protective effect on apoptotic cell death.
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Yao
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Song
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Qi
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Xi
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Chinese People's Liberation Army 210 Hospital, Dalian 116021, People's Republic of China. Electronic address: xiaoxiao270@163.com.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Huang
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: songsj99@163.com.
authors.forename: Shao-Jiang
authors.initials: SJ
authors.lastname: Song
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D032364:Daphne / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D054876:Prenylation; D013237:Stereoisomerism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D055372:AMP-Activated Protein Kinases
keywords: Apoptosis; Autophagy; Daphne giraldii; Enantiomers; Flavans