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Tumor-localized catalases fail to alter tumor growth or transcriptional profiles in mice

ABSTRACT: Catalase is an antioxidant enzyme that catalyzes the rapid conversion of hydrogen peroxide to water and oxygen. Use of catalase as a cancer therapeutic has been proposed to reduce oxidative stress and hypoxia in the tumor microenvironment, both activities which are hypothesized to reduce tumor growth. Furthermore, exposing murine tumors to exogenous catalase was previously reported to have therapeutic benefit. We studied the therapeutic effect of tumor-localized catalases with the aim to further elucidate the mechanism of action. To do this, we engineered two approaches to maximize intratumoral catalase exposure: 1) an injected extracellular catalase with enhanced tumor retention, and 2) tumor cell lines that over-express intracellular catalase. Both approaches were characterized for functionality and tested for therapeutic efficacy and mechanism in murine syngeneic tumor models. We did not observe a significant difference in tumor growth or survival between catalase-treated and untreated mice when either approach was used. Finally, bulk RNA sequencing of tumors was performed, comparing the gene expression of catalase-treated and untreated tumors. Gene expression analysis revealed very few differentially expressed genes as a result of exposure to catalase and notably, we did not observe changes consistent with an altered state of hypoxia or oxidative stress. In conclusion, we observe that sustained intratumoral catalase neither has therapeutic benefit nor triggers significant differential expression of genes associated with the anticipated therapeutic mechanism.

ORGANISM(S): Mus musculus

PROVIDER: GSE225211 | GEO | 2023/06/21

REPOSITORIES: GEO

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