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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2015

Open Access 01-12-2015 | Research

Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death

Authors: Perrine Kafara, Philippe Icard, Marilyne Guillamin, Laurent Schwartz, Hubert Lincet

Published in: Journal of Ovarian Research | Issue 1/2015

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Abstract

Background

Ovarian carcinoma is the leading cause of death from gynecological cancer because there is risk of chemoresistance. As previously demonstrated in our laboratory, Alpha-lipoic acid (LA), a co-factor for metabolic enzymes, suppresses the tumor growth. In this study, we have researched the mechanisms that are responsible for the activity of LA.

Methods

We have studied the mechanisms of LA in two ovarian cancer cell lines, a cisplatin sensitive one, IGROV1 and its resistant counterpart, IGROV1-R10. These cells have been exposed to lipoic acid at various concentrations. Cell proliferation, cell cycle repartition and nuclear staining with DAPI were recorded. Western blot analyses were performed to detect various proteins implied in apoptotic cell death pathways. To investigate the formation of ROS, the oxidation of CM-DCFH2-DA were also determined.

Findings

LA suppressed growth proliferation and induced apoptosis in both ovarian cell lines. Moreover, LA provoked a down regulation of two anti-apoptotic proteins, Mcl-1 and Bcl-xL protein and a strong induction of the BH3-only protein Bim. Furthermore, LA induced ROS generation which could be involved in the CHOP induction which is known to activate the Bim translation.

Conclusions

Our results reveal novel actions of LA which could explain the anti-tumoral effects of the LA. Therefore, LA seems to be a promising compound for ovarian cancer treatment.
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Metadata
Title
Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death
Authors
Perrine Kafara
Philippe Icard
Marilyne Guillamin
Laurent Schwartz
Hubert Lincet
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2015
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-015-0165-z

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