Search of New Cytotoxic Crude Materials Against Human Oral Squamous Cell Carcinoma Using ~1H NMR-based Metabolomics

摘要

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 (CC^q) was determined from the dose-response curve. Tumor-specificity (TS) was determined by the following equation: TS=mean CC5q (normal cells)/mean CC5q (cancer cell lines). Metabolic profiling techniques based on1!! 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.