title: Search of new cytotoxic crude materials against human oral squamous cell carcinoma using 1H NMR-based metabolomics.
abstract: BACKGROUND
  The 5-year survival rate of the oral cancer patients has remained at approximately the 50% level during the past 30 years, possibly due to the poor tumor-selectivity of conventional anticancer drugs. This prompted us to search new plant extracts that have higher cytotoxicity against cancer cells than normal cells.
  
  
  METHODS
  Two human oral squamous cell carcinoma cell lines (HSC-2 and HSC-4) and two normal oral cells (gingival and periodontal ligament fibroblasts; HGF and HPLF) were incubated for 48 h with various concentrations of crude plant extract and the viable cell number was determined by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The 50% cytotoxic concentration (CC50) was determined from the dose-response curve. Tumor-specificity (TS) was determined by the following equation: TS=mean CC50 (normal cells)/mean CC50 (cancer cell lines). Metabolic profiling techniques based on (1)H nuclear magnetic resonance (NMR) were applied to gain the chemical structural insight for cytotoxicity induction.
  
  
  RESULTS
  Among 24 plant extracts, Camptotheca acuminate leaf, a well-known source for camptothecin, showed the highest TS value (88.3), followed by Vitis s.p.p. (>3.5), Sasa veitchii (>2.3) and Phellodendron amurense (>2.1), whereas other plant extracts showed much lower TS value (<2). These cytotoxic extracts made cluster on principal component analysis (PCA) score plot.
  
  
  CONCLUSIONS
  The TS value determined by the present method seems to reflect the anti-tumor potential of each plant extract, while a part of the cytotoxic compounds present in these extracts may have common chemical structures.
authors: Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors: Ryuichiro
authors: R
authors: Suzuki
authors: Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors: Shinpei
authors: S
authors: Matsuno
authors: Division of Pharmacology, Meikai University School of Dentistry, Saitama, Japan.
authors: Hiroshi
authors: H
authors: Sakagami
authors: Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors: Yoshihito
authors: Y
authors: Okada
authors: Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan shiratak@josai.ac.jp.
authors: Yoshiaki
authors: Y
authors: Shirataki
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055432:Metabolomics; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: 1H NMR metabolomics; Crude drugs; cytotoxicity