Development of
cancer cell resistance against prooxidant drugs limits its potential clinical use. MCF-7
breast cancer cells chronically exposed to ascorbate/
menadione became resistant (Resox cells) by increasing mainly
catalase activity. Since
catalase appears as an anticancer target, the elucidation of mechanisms regulating its expression is an important issue. In MCF-7 and Resox cells, karyotype analysis showed that chromosome 11 is not altered compared to healthy mammary epithelial cells. The genomic gain of
catalase locus observed in MCF-7 and Resox cells cannot explain the differential
catalase expression. Since ROS cause DNA lesions, the activation of DNA damage signaling pathways may influence
catalase expression. However, none of the related
proteins (i.e., p53, ChK) was activated in Resox cells compared to MCF-7. The c-abl
kinase may lead to
catalase protein degradation via posttranslational modifications, but neither ubiquitination nor phosphorylation of
catalase was detected after
catalase immunoprecipitation.
Catalase mRNA levels did not decrease after
actinomycin D treatment in both cell lines. DNMT inhibitor (5-aza-2'-deoxycytidine) increased
catalase protein level in MCF-7 and its resistance to prooxidant drugs. In line with our previous report, chromatin remodeling appears as the main regulator of
catalase expression in
breast cancer after chronic exposure to an oxidative stress.