title: Cytotoxicity of dental compounds towards human oral squamous cell carcinoma and normal oral cells.
abstract: OBJECTIVE
  The cytotoxicity of four dental compounds, hydroquinone, benzoquinone, eugenol and phtharal towards human oral squamous cell carcinoma (OSCC) cell lines, normal human oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and skin keratinocytes was investigated.
  
  
  METHODS
  Viable cell number was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. The concentration that reduced the viable cells by 50% (CC(50)) and the concentration that increased the viability of UV-irradiated cells to 50% (EC(50)) were determined from the dose-response curves. The tumor-specificity index (TS) was determined by the ratio of the mean CC(50) for normal cells to the one for tumor cells. Apoptosis induction was monitored by assay of internucleosomal DNA fragmentation and caspase-3/-7 activation.
  
  
  RESULTS
  When both oral OSCC and normal oral cells were incubated for 4 h with any of hydroquinone, benzoquinone, eugenol and phtharal, irreversible cell growth inhibition, accompanied by cell death occurred without induction of apoptotic markers, although caspase-3/-7 activation was observed at 6 h or later. These compounds exhibited very low tumor-specificity (TS=0.4-1.3), as compared with anticancer drugs (5-fluorouracil, melphalan, peplomycin) (TS=4.1-9.7). Human skin keratinocytes were the most resistant to these drugs, and a long incubation time was required to induce irreversible growth inhibition. However, all dental compounds exhibited very low tumor-specificity (TS=0.4-2.4), compared to human skin keratinocytes and OSCC cell lines. None of the dental compounds exhibited any hormetic growth stimulation, nor protected the cells from UV-induced damage.
  
  
  CONCLUSIONS
  These results suggest that apoptosis is not involved in the early stage of growth inhibition induced by dental compounds.
authors.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.  sakagami@dent.meikai.ac.jp.
authors.forename: Teho
authors.initials: T
authors.lastname: Koh
authors.forename: Mamoru
authors.initials: M
authors.lastname: Machino
authors.forename: Yukio
authors.initials: Y
authors.lastname: Murakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005054:Eugenol / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009055:Mouth / Q000166:cytology / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D009910:Oral Hygiene; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D016227:Benzoquinones; D006873:Hydroquinones; D009930:Organic Chemicals; C004532:quinone; D005054:Eugenol; D053148:Caspase 3; D053179:Caspase 7; C031927:hydroquinone