Apr 9, 2015

Overexpression of Nrf2 attenuates Carmustine-induced cytotoxicity in U87MG human glioma cells

BMC Cancer
Sangeetha Sukumari-RameshKrishnan M Dhandapani

Abstract

Malignant glioma is one of the most devastating tumors in adults with poor patient prognosis. Notably, glioma often exhibits resistance to conventional chemotherapeutic approaches, complicating patient treatments. However, the molecular mediators involved in tumor chemoresistance remain poorly defined, creating a barrier to the successful management of glioma. In the present study, we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU), a widely used chemotherapeutic agent known to modulate cellular oxidative balance. To test the hypothesis, we employed human malignant glioma cell line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both pharmacological and genetic approaches. Notably, induction of Nrf2 was associated with increased expression of heme oxygenase-1 (HO-1), a stress inducible enzyme involved in anti-oxidant defense. In addition, over expression of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as evidenced by both cellular viability assay and flow cytometry analysis. Consistent with this, antioxidants such as glutathione and N-acetyl cysteine significantly redu...Continue Reading

Mentioned in this Paper

Study
Flow Cytometry
Antineoplastic Agents
Antibiotic Resistance, Neoplasm
NF-E2-Related Factor 2
Antioxidant Effect
Antioxidants
Neoplasms
Antineoplastic Agents, Alkylating
Oxidative Stress

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