Details

Autor(en) / Beteiligte

• XIAODONG ZHANG
• VARIN, Emilie
• ALLOUCHE, Stéphane
• YUNFEI LU
• POULAIN, Laurent
• ICARD, Philippe

Titel

Effect of Citrate on Malignant Pleural Mesothelioma Cells: A Synergistic Effect with Cisplatin

Ist Teil von

• Anticancer research, 2009-04, Vol.29 (4), p.1249-1254

Ort / Verlag

Attiki: International Institute of Anticancer Research

Erscheinungsjahr

2009

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Background: Because cancer cells are partly or mainly dependent on glycolysis to generate ATP (Warburg effect), any inhibition of glycolysis may slow down their proliferation or kill them. Materials and Methods: The anti-tumor effect of citrate, an inhibitor of phosphofructokinase, was tested on particularly chemoresistant MSTO-211H human mesothelioma cells. Results: A 3-day continuous exposure to citrate led to apoptotic cell death via a mitochondrial pathway, associated with a reduction of anti-apoptotic protein Bcl-x L and Mcl-1 expression. However, when citrate was removed, the remaining cells resumed their proliferation. The treatment of cells with a non-cytotoxic dose of cisplatin at the end of the citrate exposure led to a strong cytotoxicity, almost all cells being killed. Conclusion: Depletion of ATP, diminution of the expression of the anti-apoptotic proteins and inhibition of hexokinase secondary to inhibition of phosphofructokinase by citrate may explain the cytotoxic activity of this molecule and its synergistic effect with cisplatin.