title: Antitumour activity of 2-dihydroailanthone from the bark of Ailanthus altissima against U251.
abstract: Context The bark of Ailanthus altissima (Mill.) Swingle (Simaroubaceae) is traditionally used to treat ascariasis, diarrhoea, spermatorrhoea, bleeding and gastrointestinal diseases. Objective The objective of this study is to investigate the antitumour activity and mechanism of 2-dihydroailanthone isolated from A. altissima. Materials and methods The U251 cells were treated with 1.00, 4.00 and 8.00 μg/mL of 2-dihydroailanthone for 48 h and the normal cells treated with 20.00 μg/mL of 2-dihydroailanthone were tested as well. Proliferation inhibition of 2-dihydroailanthone on the cells was tested by MTT. Apoptosis and cell-cycle distribution in U251 cells with 1.00, 3.00 and 5.80 μg/mL of 2-dihydroailanthone for 48 h were determined by flow cytometry, respectively. The expression of the apoptosis-related genes and proteins was analysed by RT-PCR and Western blot method, respectively. Results MTT assay revealed that 2-dihydroailanthone inhibited U251 cells proliferation. The cell viability of U251 cells was 62.82, 31.34 and 25.58%, and that of three normal cells was 72.75, 82.74 and 44.92%, respectively. Flow cytometry assay showed that 2-dihydroailanthone induced apoptosis and G0/G1 phase cycle arrest towards U251 cells. The late apoptotic cells were 11.37, 21.73 and 33.83%, and the cells cycle distributed in the G0/G1 accounted for 48.85, 62.77 and 64.40%, respectively. The Western blot and RT-PCR assay showed that up-regulation of pro-apoptotic bax protein and down-regulation of anti-apoptotic bcl-2 protein as well as their mRNA on U251 cells might be related to the apoptosis induction and proliferation inhibition. Conclusion An important bioactive component, 2-dihydroailanthone, has antitumour effects, enlightening a novel source of phytomedicines in tumour therapy.
authors.affiliation: a Department of Medicinal Natural Product Chemistry , School of Pharmaceutical Sciences, Hebei Medical University , Shijiazhuang Hebei Province , China ;|b Hebei Province Key Laboratory of Research and Development for Chinese Medicine , Institute of Chinese Materia Medica, Chengde Medical College , Chengde , Hebei Province China ;
authors.forename: Ruxing
authors.initials: R
authors.lastname: Wang
authors.affiliation: c Basic Medical Institute, Chengde Medical College , Chengde , Hebei Province , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: c Basic Medical Institute, Chengde Medical College , Chengde , Hebei Province , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: c Basic Medical Institute, Chengde Medical College , Chengde , Hebei Province , China.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Liang
authors.affiliation: c Basic Medical Institute, Chengde Medical College , Chengde , Hebei Province , China.
authors.forename: Luyang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: a Department of Medicinal Natural Product Chemistry , School of Pharmaceutical Sciences, Hebei Medical University , Shijiazhuang Hebei Province , China ;
authors.forename: Manli
authors.initials: M
authors.lastname: Zhang
authors.affiliation: a Department of Medicinal Natural Product Chemistry , School of Pharmaceutical Sciences, Hebei Medical University , Shijiazhuang Hebei Province , China ;
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Shi
mesh_terms: D032268:Ailanthus / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D016716:PC12 Cells; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D036702:Quassins / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C000614079:2-dihydroailanthone; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D036702:Quassins; D051028:bcl-2-Associated X Protein
keywords: Apoptosis; cell cycle; glioma; quassinoid