title: Hormetic and UV-protective effects of azulene-related compounds.
abstract: BACKGROUND
  We have previously reported a possible anti-inflammatory activity of azulene-, tropolone- and azulenequinone-related compounds. To further pursue the newly discovered biological activity of these compounds, five compounds that inhibited nitric oxide production by activated macrophages were investigated for their possible hormetic and anti-radiation effects.
  
  
  METHODS
  Viable cell number of human oral normal cells (gingival fibroblast, pulp cell and periodontal ligament fibroblast) and three oral squamous cell carcinoma cell lines on treatment with various concentrations of each azulene-related compound was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Apoptosis induction was monitored by caspase-3 activation and DNA fragmentation.
  
  
  RESULTS
  Among five compounds, only benzo[b]cyclohepta[e][1,4]thiazine slightly stimulated the growth of all three normal cell types, but not tumor cell lines, at concentrations slightly higher than cytotoxic concentrations. Using a newly established evaluation system for UV-induced cellular damage, we found that this compound slightly but significantly protected the cells from UV-induced cellular injury, and its effect was synergistically enhanced by sodium ascorbate.
  
  
  CONCLUSIONS
  These data suggest the possible application of benzo[b]cyclohepta[e][1,4]thiazine in UV protection therapy.
authors.affiliation: Faculty of Science, Josai University, Sakado, Saitama 350-0295, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ueki
authors.forename: Aki
authors.initials: A
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Wakabayashi
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001205:Ascorbic Acid / Q000032:analysis; D052176:Azulenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000032:analysis; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D013473:Sunscreening Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052176:Azulenes; D013473:Sunscreening Agents; D013778:Tetrazolium Salts; D013843:Thiazines; D013844:Thiazoles; C558119:benzo(b)cyclohepta(e)(1,4)thiazine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; C022616:thiazolyl blue; D001205:Ascorbic Acid