title: Effects of TiO2 nanoparticles on cytotoxic action of chemotherapeutic drugs against a human oral squamous cell carcinoma cell line.
abstract: BACKGROUND
  Despite the rapid development of nanotechnology, the biological significance of TiO2 nanoparticles (NPs), possibly released from dental materials, is not well-understood. We investigated the effect of TiO2 NPs on the sensitivity of human oral squamous cell carcinoma (OSCC) cell line (HSC-2) to five popular chemotherapeutic agents.
  
  
  METHODS
  Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The aggregation and cellular uptake of TiO2 NPs were assessed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. Adsorption of TiO2 NPs to anticancer drugs was assessed by the antitumor activity recovered from the TiO2 NP-free supernatant.
  
  
  RESULTS
  When mixed with culture medium, TiO2 NPs instantly aggregated, and some particles were incorporated into the cells, exclusively in the vacuoles. TiO2 NPs showed no cytotoxicity nor hormetic growth stimulation at lower concentrations. Doxorubicin, melphalan, 5-fluorouracil and gefitinib were cytotoxic, whereas docetaxel was cytostatic with or without TiO2 NPs. TiO2 NPs, at wide concentration ranges (0.2-3.2 mM), did not significantly affect the adsorption of NPs to any of these anticancer drugs, nor affected their cytotoxic or cytostatic activity.
  
  
  CONCLUSIONS
  This experimental study demonstrated for the first time that TiO2 NP do not affect the antitumor potential of chemotherapeutic agents against the HSC-2 OSCC cell line.
authors.affiliation: Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. sakagami@dent.meikai.ac.jp; dentist.garcia@gmail.com.
authors.forename: Rene
authors.initials: R
authors.lastname: Garcia-Contreras
authors.forename: Rogelio J
authors.initials: RJ
authors.lastname: Scougall-Vilchis
authors.forename: Rosalia
authors.initials: R
authors.lastname: Contreras-Bulnes
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ando
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kanda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hibino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D009062:Mouth Neoplasms; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D014025:Titanium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; C009495:titanium dioxide; D014025:Titanium
keywords: TEM; TiO2 nanoparticle; cytotoxicity; oral squamous cell carcinoma