title: Effect of antioxidants, oxidants, metals and saliva on cytotoxicity induction by sodium fluoride.
abstract: We have recently found that millimolar concentrations of sodium fluoride (NaF) induced apoptotic cell death, characterized by caspase activation and DNA fragmentation, in tumor cell lines. This finding paved the way to investigating the interaction between NaF and the oral environment. As an initial step, we investigated redox compounds, metals and saliva, which may modify the cytotoxic activity of NaF against a human oral squamous cell carcinoma cell line (HSC-2). The minimum exposure time to NaF required for cytotoxicity induction was 8 hours. Noncytotoxic concentrations of antioxidants (sodium ascorbate, gallic acid, epigallocatechin gallate, chlorogenic acid, curcumin, superoxide dismutase, catalase), oxidants (hydrogen peroxide, sodium hypochlorite), metals (CuCl, CuCl2, FeCl2, FeCl3, CoCl2) or saliva neither protected against, nor enhanced the cytotoxic activity of NaF. Cytotoxic concentrations of these compounds produced somewhat additive, but not synergistic, effects on the cytotoxicity of NaF. ESR analysis demonstrated that NaF did not apparently change the radical intensity of sodium ascorbate and gallic acid, measured under alkaline conditions. During the cell death induction in human promyelocytic leukemia HL-60 cells by NaF, the consumption of glucose rapidly declined, followed by a decline in the consumption of major amino acids. The present study suggests that the cytotoxic activity of NaF is not regulated by the redox mechanism, but rather linked to the rapid decline in glucose consumption at early stage.
authors.affiliation: Department of Dental Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Sufi Reza M
authors.initials: SR
authors.lastname: Morshed
authors.forename: Sumiko
authors.initials: S
authors.lastname: Otsuki
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Takayama
authors.forename: Takao
authors.initials: T
authors.lastname: Satoh
authors.forename: Ken
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yasui
authors.forename: Satomi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Haruhide
authors.initials: H
authors.lastname: Kanegae
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yokote
authors.forename: Kiso
authors.initials: K
authors.lastname: Akahane
authors.forename: Masanori
authors.initials: M
authors.lastname: Kashimata
authors.forename: Kazue
authors.initials: K
authors.lastname: Satoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008670:Metals / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012463:Saliva / Q000737:chemistry*; D012969:Sodium Fluoride / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D008670:Metals; D016877:Oxidants; D012969:Sodium Fluoride; D005947:Glucose