Changes in the free-radical state and level of free iron during the formation of drug resistance in tumor cells
Saprin, A.N.; Kalinina, E.V.; Serezhenkov, V.A.; Kotova, I.N.; Solomka, V.S.; Shcherbak, N.P.
Biofizika 51(3): 485-490
2006
ISSN/ISBN: 0006-3029 PMID: 16808348 Document Number: 598206
The development of resistance of K562 human erythroleukemia cells to doxorubicin, a widely used antitumor antibiotic with the prooxidant action, leads to changes in the free-radical state of cells. It has been found that the formation of superoxide anion in resistant cells decreases. The introduction of doxorubicin to the culture medium induced a considerably lesser increase in the formation of O2*- in resistant cells compared to sensitive cells. At the same time, a strong decrease in the ESR signal of semiquinone type with a g-factor of 2.006 was observed in a culture of resistant cells grown in the absence of doxorubicin as compared with sensitive cells grown under similar conditions. At the same time, a decrease in the level of paramagnetic nitrosyl complexes of nonheme iron in resistant cells was recorded, indicating a decrease in the content of free nonheme iron as a result of the formation of drug resistance. In addition, a decrease in the level of mRNA of the transferrin receptor in resistant cells was found by the RT-PCR. These data indicate the development of a coodinated redox-dependent adaptive response, which makes itself evident as a suppression of free radical processes during the formation of resistance of K562 cells to doxorubicin.