title: Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer cells.
abstract: Spiramine C-D, the atisine-type diterpenoid alkaloids isolated from the Chinese herbal medicine Spiraea japonica complex, are shown to have anti-inflammatory effects in vitro. In this study, we report that spiramine derivatives of spiramine C-D bearing α,β-unsaturated ketone induce apoptosis of Bax(-/-)/Bak(-/-) MEFs cell, which is positively corresponding their cytotoxicity of tumor cell lines including multidrug resistance MCF-7/ADR. The results indicated that oxazolidine ring is necessary, and derivatives bearing double 'Michael reaction acceptor' group would significantly increased activities both of inducing apoptosis of Bax(-/-)/Bak(-/-) cells and cytotoxicity of tumor cells. The result indicated that spiramine derivative with α,β-unsaturated ketone group is a new anti-cancer agent with a capability of inducing apoptosis of cancer cells in Bax/Bak-independent manner.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China; The Key Laboratory of Chemistry for Natural Product of Guizhou Province, Chinese Academy of Science, Beijing 100101, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, RP China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Hong-Chun
authors.initials: HC
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China.
authors.forename: Duo-Zhi
authors.initials: DZ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Geng
authors.affiliation: The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, RP China. Electronic address: chenq@ioz.ac.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China. Electronic address: haoxj@mail.kib.ac.cn.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Hao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D017353:Gene Deletion; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D031992:Spiraea / Q000737:chemistry; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000187:drug effects* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000187:drug effects* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C000592452:spiramine C; C000592453:spiramine D
keywords: Apoptosis; Bax(−/−)/Bak(−/−) cells; Cytotoxicity; Spiramine derivative; α,β-Unsaturated ketone