title: New biological activities of Rhinacanthins from the root of Rhinacanthus nasutus.
abstract: BACKGROUND
  We recently reported that the ethyl acetate (EtOAc)-soluble fraction of the methanol extract of the root of Rhinacanthus nasutus showed tumor-specific non-apoptotic cytotoxicity and antiosteoclastogenic activity. In the present study, we investigated whether five rhinacanthins, mostly isolated from the EtOAc-soluble fraction of this plant, are responsible for these activities.
  
  
  METHODS
  The cytotoxic activity was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. The 50% cytotoxic concentration (CC(50)) was determined by the dose-response curve. Tumor specificity (TS) was determined by the ratio of the mean CC(50) for normal cells to that of tumor cell lines. DNA fragmentation was assayed by agarose gel electrophoresis. Caspase-3 activation was monitored by substrate cleavage assay. Osteoclastogenesis was monitored by tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of NF-κB ligand (RANKL)-stimulated bone marrow-derived macrophages.
  
  
  RESULTS
  Among five rhinacanthins (rhinacanthin C, G, N and Q, and rhinacanthone), rhinacanthin C exhibited the highest tumor specificity (TS=15.2). Rhinacanthin C did not induce internucleosomal DNA fragmentation nor caspase-3 activation, suggesting non-apoptotic cell death. Rhinacanthin C most potently inhibited the RANKL-stimulated osteoclastogenesis.
  
  
  CONCLUSIONS
  The present study suggests that rhinacanthin C may be responsible for the biological activity of the EtOAc-soluble fraction prepared from the methanolic extract of R. nasutus we previously reported on.
authors: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. shiratak@josai.ac.jp
authors: Haruka
authors: H
authors: Horii
authors: Ryuichiro
authors: R
authors: Suzuki
authors: Hiroshi
authors: H
authors: Sakagami
authors: Mineko
authors: M
authors: Tomomura
authors: Akito
authors: A
authors: Tomomura
authors: Yoshiaki
authors: Y
authors: Shirataki
mesh_terms: D027901:Acanthaceae / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D010936:Plant Extracts; C515073:rhinacanthin-C