Original scientific paper
https://doi.org/10.3325/cmj.2014.55.206
Specific antioxidant compounds differentially modulate cytotoxic activity of doxorubicin and cisplatin: in vitro and in vivo study
Rostyslav Panchuk
; Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Nadia Skorokhyd
; Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Vira Chumak
; Ivan Franko Lviv Nation University, Lviv, Ukraine
Lilya Lehka
; Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Sofya Omelyanchik
; Center of Food, National Academy of Sciences of Belarus (Grodno Branch), Grodno, Belarus
Valery Gurinovich
; Center of Food, National Academy of Sciences of Belarus (Grodno Branch), Grodno, Belarus
Andrey Moiseenok
; Center of Food, National Academy of Sciences of Belarus (Grodno Branch), Grodno, Belarus
Petra Heffeter
; Institute of Cancer Research Vienna Medical University, Vienna Austria
Walter Berger
; Institute of Cancer Research Vienna Medical University, Vienna Austria
Rostyslav Stoika
; Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Abstract
Aim 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.
Conclusion 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.
Keywords
Hrčak ID:
129836
URI
Publication date:
15.6.2014.
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