title: Catalase overexpression in mammary cancer cells leads to a less aggressive phenotype and an altered response to chemotherapy.
abstract: Because reactive oxygen species (ROS) are naturally produced as a consequence of aerobic metabolism, cells have developed a sophisticated set of antioxidant molecules to prevent the toxic accumulation of these species. However, compared with normal cells, malignant cells often exhibit increased levels of intracellular ROS and altered levels of antioxidant molecules. The resulting endogenous oxidative stress favors tumor growth by promoting genetic instability, cell proliferation and angiogenesis. In this context, we assessed the influence of catalase overexpression on the sensitivity of breast cancer cells towards various anticancer treatments. Our data show that catalase overexpression in MCF-7 cells leads to a 7-fold increase in catalase activity but provokes a 40% decrease in the expression of both glutathione peroxidase and peroxiredoxin II. Interestingly, proliferation and migration capacities of MCF-7 cells were impaired by the overexpression of catalase, as compared to parental cells. Regarding their sensitivity to anticancer treatments, we observed that cells overexpressing catalase were more sensitive to paclitaxel, etoposide and arsenic trioxide. However, no effect was observed on the cytotoxic response to ionizing radiations, 5-fluorouracil, cisplatin or doxorubicin. Finally, we observed that catalase overexpression protects cancer cells against the pro-oxidant combination of ascorbate and menadione, suggesting that changes in the expression of antioxidant enzymes could be a mechanism of resistance of cancer cells towards redox-based chemotherapeutic drugs.
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Glorieux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dejeans
authors.forename: Brice
authors.initials: B
authors.lastname: Sid
authors.forename: Raphaël
authors.initials: R
authors.lastname: Beck
authors.forename: Pedro Buc
authors.initials: PB
authors.lastname: Calderon
authors.forename: Julien
authors.initials: J
authors.lastname: Verrax
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014965:X-Rays
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D002374:Catalase