Modulation of branching morphogenesis of fetal mouse submandibular gland by sodium ascorbate and epigallocatechin gallate.

As an initial step to study the effect of antioxidants on the oral environment, we here investigated how sodium ascorbate and (-)-epigallocatechin 3-O-gallate (EGCG) affect the branching morphogenesis of the fetal mouse submandibular gland (SMG). When mouse SMG was prepared from the embryo at 13-day post prenatal stage and cultured, gradual development of branching morphogenesis was observed. Addition of sodium ascorbate affected this morphological change in a bimodal fashion. At lower concentrations of sodium ascorbate (0.25 approximately 2.27 mM), the branching morphogenesis was slightly but significantly (about 60%) enhanced, whereas at higher concentrations of sodium ascorbate (6.82 approximately 10.1 mM), the branching morphogenesis was inhibited. The addition of EGCG failed to stimulate, but inhibited the branching morphogenesis in a dose-dependent manner. These data support that the addition of a lower concentration of sodium ascorbate is essential to stimulate the growth of SMG, and that sodium ascorbate, but not all antioxidants, induces hormesis (beneficial action at lower concentration) in the present SMG system.

Inhibition of branching morphogenesis of mouse fetal submandibular gland by sodium fluoride--protection by epidermal growth factor.

As an initial step to study the effect of sodium fluoride on the oral environment, we investigated how sodium fluoride (NaF) affects the branching morphogenesis of fetal mouse submandibular gland (SMG). When mouse SMG was prepared from the embryo at 13 days post prenatal stage and cultured, gradual development of branching morphogenesis was observed. Addition of NaF affected this morphological change in bimodal fashions. At a lower concentration of NaF (< 2 microM), the branching morphogenesis was slightly enhanced, whereas at a higher concentration of NaF (4 - 8 microM), it was almost completely inhibited. The inhibitory effect of NaF at the higher concentration was abrogated by stimultaneous addition of epidermal growth factor (EGF), but not by 5alpha-dihydrotestosterone (DHT) or insulin-like growth factor (IGF). These data demonstrate that EGF can effectively reduce the cytotoxic activity of NaF at micromolar concentration.

Cytotoxic and multidrug resistance reversal activity of a vegetable, 'Anastasia Red', a variety of sweet pepper.

The vegetable, Anastasia Red, Capsicum annuum L. var. angulosum Mill. (Solanaceae) was successively extracted with hexane, acetone, methanol and 70% methanol, and the extracts were further separated into a total of 21 fractions by silica gel or octadecylsilane (ODS) column chromatography. The biological activities of extracts and fractions were determined. These extracts showed relatively higher cytotoxic activity against two human oral tumor cell lines (HSC-2, HSG) than against normal human gingival fibroblasts (HGF), suggesting a tumor-specific cytotoxic activity. The cytotoxic activity of these extracts was enhanced by fractionation on silica gel [H2, A2, M1-M3] or ODS column chromatography [70M]. Several fractions [H2, H4, H5, A1, A2, A3, A5, A6, A7, M2] reversed the multidrug resistance (MDR) phenotype with L5178 mouse lymphoma T cells, more efficiently than (+/-)-verapamil. The extracts and fractions did not show any detectable anti-human immunodeficiency virus (HIV) or anti-Helicobacter pylori activity. Thus, this study suggests the effective and selective antitumor potential of 'Anastasia Red' of sweet pepper for further phytochemical and biological investigation.