Inhibition of Mcl-1 expression by citrate enhances the effect of Bcl-xL inhibitors on human ovarian carcinoma cells

Journal of Ovarian Research

Philippe Icard¹  Laurent Poulain²  Marie-Hélène Louis²  Maryline Duval²  Edwige Abeilard-Lemoisson²  Florence Giffard²  Perrine Kafara²  Hubert Lincet² 

[1] Service de Chirurgie Thoracique, Centre Hospitalier Universitaire de Caen Basse-Normandie, Avenue de la Côte de Nacre, Caen 14000, France;Centre de Lutte Contre le Cancer François Baclesse, Avenue du Général Harris, Caen, BP5026 14076, Cedex 05, France

关键词: Cell death;    Ovarian cancer;    Bcl-x_L;    Citrate;    Mcl-1;   

Others  :  805299
DOI  :  10.1186/1757-2215-6-72

 received in 2013-06-17, accepted in 2013-10-04,  发布年份 2013

【 摘 要 】

The inhibition of two major anti-apoptotic proteins, Bcl-x_L and Mcl-1, appears essential to destroy chemoresistant cancer cells. We have studied their concomitant inhibition, using ABT 737 or siRNA targeting XL1 and citrate, a molecule which reduces the expression level of Mcl-1.

Two cisplatin-chemoresistant ovarian cell lines (SKOV3 and IGROV1-R10) were exposed to ABT 737 or siRNA targeting XL1 and citrate at various individual concentrations, or combined. 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.

Mcl-1 expression was barely reduced when cells were exposed to citrate alone, whereas a mild reduction was observed after ABT 737 treatment. Concomitant inhibition of Bcl-x_L and Mcl-1 using ABT 737 or siXL1 associated with citrate was far more effective in inhibiting cell proliferation and inducing cell death than treatment alone.

Given that few, if any, specific inhibitors of Mcl-1 are currently available, anti-glycolytic agents such as citrate could be tested in association with synthetic inhibitors of Bcl-x_L.

【 授权许可】

   
2013 Lincet et al.; licensee BioMed Central Ltd.

【 图 表 】

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