title: Cytotoxicity and type of cell death induced by local anesthetics in human oral normal and tumor cells.
abstract: BACKGROUND
  Local anesthetics are often administered to tumors and surrounding tissues during the surgery of the head and neck area, however their effects on oral tissues is not well understood. In the present study, the cytotoxicity of a total of seven local anesthetics towards oral tumor and normal cells was compared.
  
  
  METHODS
  Tumor-specificity index was determined by the ratio of the mean 50% cytotoxic concentration against normal cells to that for tumor cells. Apoptosis induction was monitored by internucleosomal DNA fragmentation and caspase-3, -8, and - 9 activation. Fine cell structure was observed under transmission electron microscopy.
  
  
  RESULTS
  All local anesthetics showed slightly higher cytotoxicity towards oral squamous cell carcinoma (OSCC) cell lines than towards normal oral cells. Dibucaine, with a log p-value of approximately 3, was the most cytotoxic, followed by tetracaine, bupivacaine or ethylaminobenzoate, whereas lidocaine, procaine and mepivacain were much less cytotoxic. When the tumor-specificity was evaluated between OSCC and human skin keratinocytes, the index was 6.6. Dibucaine did not induce apoptosis of OSCC cells. On the other hand, dibucaine did induce mitochondrial injury and swelling, formation of secondary lysosomes, and at high concentrations, rupture of the cell membrane. Autophagy inhibitors did not reduce the cytotoxicity of dibucaine.
  
  
  CONCLUSIONS
  Necrosis may be involved in the induction of antitumor activity by dibucaine.
authors: Division of Anesthesiology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
authors: Katsue
authors: K
authors: Kobayashi
authors: Seika
authors: S
authors: Ohno
authors: Shigenori
authors: S
authors: Uchida
authors: Osamu
authors: O
authors: Amano
authors: Hiroshi
authors: H
authors: Sakagami
authors: Hiroshi
authors: H
authors: Nagasaka
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003992:Dibucaine / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D018922:HL-60 Cells; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000779:Anesthetics, Local; D003992:Dibucaine