[Role of the antioxidant system and redox-dependent regulation of transcription factors bcl-2 and p53 in forming resistance of human K562 erythroleukemia cells to doxorubicin].
Prooxidant effect of chemotherapeutic agents is of significant interest in connection with activation of oxidative stress in cancer cells. Role of development of adaptive antioxidant response to the rise of resistance to cytotoxical effect of doxorubicin (DOX) has been studied in human erythroleukemia K562 cells. Growth of resistance to DOX caused enhancement of antioxidant enzymes (Cu, Zn-SOD, Mn-SOD, catalase) elevation of Mn-SOD activity being predominant. Additional increasing of antioxidant level was elevation of GSH maintenance and level of GST-related enzymes (glutathione peroxidase, glutathione S-transferase, glutathione reductase) in resistance K562/DOX cells. The enhancement of antioxidant system prevented activation of lipid peroxidation. Furthermore, the antioxidant growth caused decrease of level of proteintyrosine kinases, thioredoxin, thioredoxin reductase in contrary to elevation of glutaredoxin activity. Increasing of Bcl-2 and suppression of p53 levels was found to be caused by the change of redox state of K562DOX cells. The data support the suggestion that adaptive antioxidant response to prooxidant effect of DOX promotes the development of cellular drug resistance.
Kalinina
E V
EV
Institute of Chemical Physics, Russian Academy of Sciences, Moscow.
Saprin
A N
AN
Solomka
V S
VS
Shcherbak
N P
NP
Chermnykh
N S
NS
Piruzian
L A
LA
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase
Rol' antioksidantnoĭ sistemy i redoks-zavisimoĭ reguliatsii transkriptsionnykh faktorov bcl-2 i p53 formirovanii rezistentnosti kletok K562 éritroleĭkemii cheloveka k doksorubitsinu.