title: Inhibitory activities of Lignum Sappan extractives on growth and growth-related signaling of tumor cells.
abstract: OBJECTIVE
  To investigate the active constituents of Lignum Sappan (Caesalpinia sappan L.) on growth-related signaling and cell mitosis.
  
  
  METHODS
  The influence of the ethyl acetate (EtOAc) extract of Lignum Sappan and its constituents on growth-related signaling were evaluated by a luciferase assay in cells stably-transfected with NF-κB, STAT1, or STAT3 responsive luciferase reporter plasmid. The inhibitory effect on the cell cycle was determined by flow cytometric analysis. The anti-tumor activities were assessed in vitro and in vivo.
  
  
  RESULTS
  The EtOAc extract of Lignum Sappan had inhibitory activities on growth-related signaling and cell mitosis. Three major active compounds were sappanchalcone, brazilin, and butein. Sappanchalcone blocked cell cycle progression in the G2/M phase, brazilin inhibited TNFα/NF-κB signaling, while butein inhibited IL-6/STAT3 signaling, as well as TNFα/NF-κB signaling. The three compounds all demonstrated cytotoxic activities against human tumor cells in vitro. In a S180 tumor cell-bearing mice model, the anti-tumor efficacy of the EtOAc extract was better than the individual compounds acting alone.
  
  
  CONCLUSIONS
  These results indicate that Lignum Sappan contains multiple active compounds with different antitumor activities, which act synergistically to enhance their anti-tumor effects. The EtOAc extract of Lignum Sappan may be better than individual active constituent as a novel medicine for the treatment of cancer.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jing-Li
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Qi
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Qi
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: qyu@sibs.ac.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D029911:Caesalpinia; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D047188:Chalcones; D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C040918:butein; C044363:sappanchalcone; C044362:brazilin
keywords: Anti-tumor activity; Caesalpinia sappan L.; Cell cycle blocker; Lignum Sappan; Signaling pathway inhibitor; Synergy