title: Changes of metabolic profiles in an oral squamous cell carcinoma cell line induced by eugenol.
abstract: BACKGROUND
  We have recently reported that eugenol exerted indiscriminate cytotoxicity towards normal oral cells and oral squamous cell carcinoma (OSCC) cell lines without induction of apoptosis markers. In order to investigate the underlying mechanisms of cytotoxicity induction, we investigated the effect of short-term treatment with eugenol on the metabolic profiles of a human OSCC cell line (HSC-2).
  
  
  METHODS
  The viable cell number was determined by direct cell counting with a hemocytometer after trypsinization. After washing with 5% D-mannitol solution (found to retain the highest amounts of intracellular metabolites among several washing conditions), cellular metabolites were extracted with methanol with internal markers and then subjected to metabolomic analysis.
  
  
  RESULTS
  Cytotoxic concentrations of eugenol induced the reduction of ATP utilization (assessed by a significant reduction of the AMP/ATP and ADP/ATP ratio), of oxidative stress (assessed by the increase in oxidized form of glutathione, cysteine-glutathione disulfide and methionine sulfoxide), and an increase in the polyamines and glycolytic metabolites.
  
  
  CONCLUSIONS
  The metabolic changes observed in this study suggest the induction of non-apoptotic cell death by eugenol.
authors: Division of Oral Diagnosis, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
authors: Teho
authors: T
authors: Koh
authors: Yukio
authors: Y
authors: Murakami
authors: Shoji
authors: S
authors: Tanaka
authors: Mamoru
authors: M
authors: Machino
authors: Hiromi
authors: H
authors: Onuma
authors: Miku
authors: M
authors: Kaneko
authors: Masahiro
authors: M
authors: Sugimoto
authors: Tomoyoshi
authors: T
authors: Soga
authors: Masaru
authors: M
authors: Tomita
authors: Hiroshi
authors: H
authors: Sakagami
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D005054:Eugenol / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D015317:Biogenic Polyamines; D005054:Eugenol; C031586:cysteine-glutathione disulfide; D000255:Adenosine Triphosphate; D008715:Methionine; D005978:Glutathione; D003545:Cysteine; C013111:methionine sulfoxide