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Cancer Chemotherapy and Pharmacology

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01.09.2009 | Original Article

Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts

verfasst von: Vilma A. Sardão, Paulo J. Oliveira, Jon Holy, Catarina R. Oliveira, Kendall B. Wallace

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2009

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Abstract

Purpose

Doxorubicin (DOX) is a widely prescribed chemotherapeutic. The hypothesis for the present study is that DOX-induced myocyte apoptosis involves mitochondrial dysfunction that is a consequence of nuclear DOX effects.

Methods

H9c2 myoblasts were incubated with 0, 0.5 and 1 μM DOX and nuclear and mitochondrial alterations were determined.

Results

Doxorubicin accumulation in the nucleus was detected after 3 h treatment, followed by an increase in p53 and a decrease in mitochondrial membrane potential. Apoptotic markers, such as caspase activation and chromatin condensation were detected after 24 h of DOX treatment. Bax and p53 translocation to mitochondria as well as the formation of Bax clusters in the cytosol were observed. Importantly, pifithrin-alpha, a p53 inhibitor, protected against DOX-induced mitochondrial depolarization, caspase activation and cell death.

Conclusion

Mitochondrial dysfunction in H9c2 myoblasts treated with DOX is a consequence of nuclear p53 activation rather than a direct effect of the drug on mitochondria.

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Titel: Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts
verfasst von: Vilma A. Sardão
Paulo J. Oliveira
Jon Holy
Catarina R. Oliveira
Kendall B. Wallace
Publikationsdatum: 01.09.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2009
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-0932-x

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Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts

Abstract

Purpose

Methods

Results

Conclusion

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Abstract

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Conclusion

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