[Changes in the free-radical state and level of free iron during the formation of drug resistance in tumor cells].
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.
Saprin
A N
AN
Kalinina
E V
EV
Serezhenkov
V A
VA
Kotova
Ia N
IaN
Solomka
V S
VS
Shcherbak
N P
NP
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007501:Iron / Q000378:metabolism*; D020014:K562 Cells; D009589:Nitrogen Oxides / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D009589:Nitrogen Oxides; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D013481:Superoxides; C073661:dinitrosyl iron complex; D004317:Doxorubicin; D007501:Iron