title: Specific antioxidant compounds differentially modulate cytotoxic activity of doxorubicin and cisplatin: in vitro and in vivo study.
abstract: OBJECTIVE
  To use the antioxidant compounds (sodium selenite, selenomethionine, D-pantethine) for modulation of cytotoxic effect of doxorubicin and cisplatin toward wild type and drug-resistant mutants of several human tumor cells. Similar treatments were applied in vivo toward adult male Wistar rats.
  
  
  METHODS
  Human tumor cells of different lines (HCT-116, Jurkat and HL-60) with various mechanisms of drug-resistance were treated with doxorubicin or cisplatin, alone or in combination with sodium selenite, selenomethionine, or D-pantethine. Cell viability, induction of apoptosis, and production of O2- radicals were measured. Activity of redox potential modulating enzymes was measured in the liver and blood plasma of adult male Wistar rats subjected to similar treatments.
  
  
  RESULTS
  All antioxidants used in physiologically harmless concentration inhibited cytotoxic action of doxorubicin toward tumor cells sensitive to chemotherapy treatment by 15%-30%, and slightly enhanced cytotoxic effect of this medicine toward drug-resistant malignant cells. At the same time, there was no significant effect of these antioxidants on cisplatin action. Such effects were accompanied by a complete inhibition of production of superoxide radicals induced by doxorubicin. The results of in vivo study in adult male Wistar rats were in agreement with the results of in vitro study of human tumor cells.
  
  
  CONCLUSIONS
  Protective effect of specific antioxidant agents during cytotoxic action of doxorubicin was demonstrated in vitro in drug-sensitive human tumor cells and in adult male Wistar rats, while there was no protective effect in drug-resistant sub-lines of these tumor cells during action of doxorubicin and cisplatin.
authors.affiliation: Rostyslav Panchuk, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov Street 14/16, 79005, Lviv, Ukraine, rpanchuk@ukr.net.
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Panchuk
authors.forename: Nadia
authors.initials: N
authors.lastname: Skorokhyd
authors.forename: Vira
authors.initials: V
authors.lastname: Chumak
authors.forename: Lilya
authors.initials: L
authors.lastname: Lehka
authors.forename: Sofya
authors.initials: S
authors.lastname: Omelyanchik
authors.forename: Valery
authors.initials: V
authors.lastname: Gurinovich
authors.forename: Andrey
authors.initials: A
authors.lastname: Moiseenok
authors.forename: Petra
authors.initials: P
authors.lastname: Heffeter
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Stoika
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012645:Selenomethionine / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D010204:Pantetheine; C005425:pantethine; D004317:Doxorubicin; D012645:Selenomethionine; D010088:Oxidoreductases; D018038:Sodium Selenite; D002945:Cisplatin