title: Topoisomerase II inhibitors from the roots of Stellera chamaejasme L.
abstract: Three new compounds, including one daphnane diterpene (1), one sesquiterpene (6), and one lignan (7) have been isolated from the Stellera chamaejasme L., together with five other known compounds, including four daphnane diterpenenoids (2-5) and one lignan (8). The structures of the new compounds were elucidated by spectroscopic analysis. The cytotoxicities of compounds 1-8 towards human lung adenocarcinoma cells (A549 cells) were evaluated using a sulforhodamine B assay. All of the compounds displayed significant cytotoxicity, with IC₅₀ values in the ranging of 0.2 nM to 2.0 μM. Mechanistic studies revealed that the antitumor activities of compounds 1-3 and 7 were derived from their inhibition of topoisomerase II (Topo II). Furthermore, as a Topo II inhibitor, compound 1 was found to effectively induced G2-M phase cell cycle arrest and apoptosis in cancer cells.
authors.affiliation: School of Life Science & Technology, Tongji University, Shanghai 200092, PR China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liu
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Han
authors.affiliation: School of Life Science & Technology, Tongji University, Shanghai 200092, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Life Science & Technology, Tongji University, Shanghai 200092, PR China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Lin-Jiang
authors.initials: LJ
authors.lastname: Tong
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Peng
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China. Electronic address: hxie@simm.ac.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China. Electronic address: suozhang@mail.shcnc.ac.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.affiliation: School of Life Science & Technology, Tongji University, Shanghai 200092, PR China. Electronic address: hbwang@tongji.edu.cn.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D029645:Thymelaeaceae / Q000737:chemistry* / Q000378:metabolism; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II
keywords: Apoptosis; Cytotoxic activity; Stellera chamaejasme L.; Topoisomerase II