0000000000535896
AUTHOR
Stefanie Huelsenbeck
showing 3 related works from this author
Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.
2012
To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia m…
The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity.
2012
Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress respo…
Chronic heart damage following doxorubicin treatment is alleviated by lovastatin.
2014
The anticancer efficacy of anthracyclines is limited by cumulative dose-dependent early and delayed cardiotoxicity resulting in congestive heart failure. Mechanisms responsible for anthracycline-induced heart damage are controversially discussed and effective preventive measures are preferable. Here, we analyzed the influence of the lipid lowering drug lovastatin on anthracycline-induced late cardiotoxicity three month after treatment of C57BL/6 mice with five low doses of doxorubicin (5×3mg/kg BW; i.p.). Doxorubicin increased the cardiac mRNA levels of BNP, IL-6 and CTGF, while the expression of ANP remained unchanged. Lovastatin counteracted these persisting cardiac stress responses evoke…