title: The Effect of Ascorbic Acid over the Etoposide- and Temozolomide-Mediated Cytotoxicity in Glioblastoma Cell Culture: A Molecular Study.
abstract: OBJECTIVE
  Glioblastoma (GBM) is one of the lethal central nervous system tumors. One of the widely used chemical agents for the treatment of glioblastoma is temozolomide. It is an orally administered, deoxyribonucleic acid (DNA) alkylating agent. DNA alkylation triggers the death of tumor cells. However, some tumor cells are able to repair this type of DNA damage and thus lower the therapeutic effect of temozolomide. Laboratory and clinical studies indicate that temozolomide"s anticancer effects might be strengthened when combined with other chemotherapeutic agents like etoposide or antioxidant agents like ascorbic acid. In this study, we aimed to evaluate the cytotoxic and oxidative stress effects of ascorbic acid (1000 ?M), temozolomide (100 ?M) and etoposide (25 ?M) agents alone and in dual and triple combinations in a glioblastoma U87 MG cell culture.
  
  
  METHODS
  The cytotoxic and oxidative stress effects were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) and liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis methods.
  
  
  RESULTS
  Cytotoxicity tests showed that etoposide, temozolomide, "etoposide+ascorbic acid", "temozolomide+ascorbic acid", "temozolomide+etoposide" and "temozolomide+etoposide+ascorbic acid" combinations have anti-proliferative effects. The maximum anti-proliferation response was observed in the "temozolomide+etoposide+ascorbic acid"-added group. Similarly LCMS/ MS analyses showed that minimum oxidative DNA damage occurred in the "temozolomide+etoposide+ascorbic acid"-added group.
  
  
  CONCLUSIONS
  Ascorbic acid decreases the cytotoxic and genotoxic effect of etoposide and etoposide-temozolomide combination but it has no meaningful effect on temozolomide"s toxicity.
authors.affiliation: Adana Science and Technology University, Faculty of Engineering and Natural Sciences, Department of Bioengineering, Adana, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Gokturk
authors.forename: Hasim
authors.initials: H
authors.lastname: Kelebek
authors.forename: Seda
authors.initials: S
authors.lastname: Ceylan
authors.forename: Dervis Mansuri
authors.initials: DM
authors.lastname: Yilmaz
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000633:toxicity*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005047:Etoposide; D003606:Dacarbazine; D001205:Ascorbic Acid; D000077204:Temozolomide