Search of new cytotoxic crude materials against human oral squamous cell carcinoma using 1H NMR-based metabolomics

Anticancer Res. 2014 Aug;34(8):4117-20.

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.

Materials and 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.

Conclusion: 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.

Keywords: 1H NMR metabolomics; Crude drugs; cytotoxicity.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Metabolomics*
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Plant Extracts / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts