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

Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 BioTICLA - Biologie et Thérapies Innovantes des Cancers Localement Agressifs UNICAEN - Université Caen Normandie, CRLCC François Baclesse, INSERM - Institut National de la Santé et de la Recherche Médicale : U1199 2 LIX - Laboratoire d-informatique de l-École polytechnique Palaiseau 3 ISPB - Institut des Sciences Pharmaceutiques et Biologiques 4 CRCL - Centre de Recherche en Cancérologie de Lyon

Abstract : 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. 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. 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. 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.

Keywords : ROS Findings ovarian cancer Lipoic acid Mcl-1 Bcl-x L Bim

Autor: Perrine Kafara - Philippe Icard - Marilyne Guillamin - Laurent Schwartz - Hubert Lincet -



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