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- Title
Changes in expression of genes encoding antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and in level of reactive oxygen species in tumor cells resistant to doxorubicin.
- Authors
Kalinina, E. V.; Chernov, N. N.; Saprin, A. N.; Kotova, Ya. N.; Andreev, Ya. A.; Solomka, V. S.; Scherbak, N. P.
- Abstract
The relationship between expression of genes encoding key antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and change in production of reactive oxygen species (ROS) resulting from development of resistance of cancer cells K562, MCF-7, and SKOV-3 to the prooxidant chemotherapeutic agent doxorubicin (DOX) has been studied. Significant increase in mRNA level and activity of Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase-1 (GPx-1) and reduced ROS level was found in resistant K562/DOX and SKVLB cells. In contrast, no change in ROS level was observed in MCF-7/DOX cells in parallel with decrease in Mn-SOD and catalase mRNAs and corresponding activities concurrently with high increase in GPx-1 mRNA and activity. As a result of the development of resistance, a similarity was found between the change in ROS level and the change in ho-1 and bcl-2 gene expression, whereas elevation of bcl-xl gene expression was observed in all three types of resistant cells. Particular features of development of adaptive antioxidant response as well as redox-dependent change in bcl-2 gene expression under formation of DOX resistance of cancer cells of different genesis are discussed.
- Subjects
DOXORUBICIN; DRUG resistance in cancer cells; GENE expression; HEME oxygenase; DRUG therapy; ANTIOXIDANTS
- Publication
Biochemistry (00062979), 2006, Vol 71, Issue 11, p1200
- ISSN
0006-2979
- Publication type
Article
- DOI
10.1134/S0006297906110058