Induction of apoptosis by flavones, flavonols (3-hydroxyflavones) and isoprenoid-substituted flavonoids in human oral tumor cell lines

Various flavones, flavonols (3-hydroxyflavones) and isoprenoid-substituted flavones (flavonols) were investigated for their cytotoxic activity. Most o f these compounds were more cytotoxic against human oral squamous cell carc inoma and salivary gland tumor cell lines than human gingival fibroblasts. The cytotoxic activity of flavonoids was generally higher than that of tann in-related compounds. Flavonoids induced apoptotic cell death characterized by DNA fragmentation (as identified by TUNEL method) and activation of cas pase(s) (as identified by degradation products of cytokeratin 18 with M30 m onoclonal antibody). ESR spectroscopy revealed that higher concentrations o f flavonoids produced radicals under alkaline conditions. However, not all of them enhanced the radical intensity of sodium ascorbate, suggesting that the redox potential of flavonoids differs considerably from samples to sam ples. Catalase failed to eliminate the cytotoxic activity of flavonoids, re ducing the possibility of the involvement of hydrogen peroxide for the cyto toxicity induction by them.