XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
103.
THE effECTIvENESS of oraCIN IN ENHaNCING THE CYTOTOXICITY
of DOXOrUBICIN THrOUGH THE INHIBITION of DOXOrUBICIN
DEaCTIvaTION IN breaST caNCEr CELL LINE MCF-7
Veronika Hanušová 1 , Lenka Vildová 1 , Věra Králová 2 , Ladislava Schröterová 2 ,
Lenka Trilecová 3 , Alena Pakostová 1 and Lenka Skálová 1
1
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec
Králové, Czech Republic, 2 Department of Biology, Faculty of Medicine,
Charles University, Hradec Králové, Czech Republic 3 Veterinary Research Institute,
Brno, Czech Republic
Doxorubicin (DOX) has played a key role in the treatment of breast cancer, but the clinical
utility of this agent is strictly limited by his associated toxicities, especially cardiotoxicity.
In present project was studied the possibilities of inhibition of the DOX reduction in breast
cancer cell line MCF7, one possible strategy to improve DOX efficacy. DOX is deactivated
mainly by the action of carbonyl reductases in MCF-7. Oracin (ORC, 6-[2-(2-hydroxyethyl)
aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno[1,2-c] isoquinoline) significantly inhibited
DOX reduction in MCF-7 cytosol. The cytotoxicity of DOX, ORC and DOX+ORC combinations
in MCF7 cells was assayed using three different end-point tests of cell viability. In
all DOX+ORC combinations, only non-cytotoxic ORC concentrations were used to avoid
the possible additive toxic effect of ORC. After a 48-hour exposition, DOX together with
ORC was able to kill 55 % more cells than DOX alone. All DOX+ORC combinations were
more toxic in rapidly proliferating cells than in slowly proliferating cells. ORC significantly
increases DOX efficacy in MCF-7 cells, probably due to the inhibition of DOX reductases.
Results suggest that concomitant use of ORC and DOX may improve the therapeutic index
of DOX in the managements of breast cancer.
228 XXII. Biochemistry Congress, Martin