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Cancer Cell International

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Open Access 01-12-2015 | Primary research

Etoposide induces cell death via mitochondrial-dependent actions of p53

Authors: Sarwat Jamil, Irene Lam, Maryam Majd, Shu-Huei Tsai, Vincent Duronio

Published in: Cancer Cell International | Issue 1/2015

Abstract

Background

Etoposide has been used clinically in cancer treatment, as well as in numerous research studies, for many years. However, there is incomplete information about its exact mechanism of action in induction of cell death.

Methods

Etoposide was compared at various concentrations to characterize the mechanisms by which it induces cell death. We investigated its effects on mouse embryonic fibroblasts (MEFs) and focused on both transcriptional and non-transcriptional responses of p53.

Results

Here we demonstrate that treatment of MEFs with higher concentrations of etoposide induce apoptosis and activate the transcription-dependent functions of p53. Interestingly, lower concentrations of etoposide also induced apoptosis, but without any evidence of p53-dependent transcription up-regulation. Treatment of MEFs with an inhibitor of p53, Pifithrin-α, blocked p53-dependent transcription but failed to rescue the cells from etoposide-induced apoptosis. Treatment with PES, which inhibits the mitochondrial arm of the p53 pathway inhibited etoposide-induced cell death at all concentrations tested.

Conclusions

We have demonstrated that transcriptional functions of p53 are dispensable for etoposide-induced cell death. The more recently characterized effects of p53 at the mitochondria, likely involving its interactions with BCL-2 family members, are thus more important for etoposide’s actions.

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Title: Etoposide induces cell death via mitochondrial-dependent actions of p53
Authors: Sarwat Jamil
Irene Lam
Maryam Majd
Shu-Huei Tsai
Vincent Duronio
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-015-0231-z

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Abstract

Background

Methods

Results

Conclusions

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