Details

Autor(en) / Beteiligte

• Lu, Yunfei
• Zhang, Xiaodong
• Zhang, Haitian
• Lan, Jiao
• Huang, Guangwu
• Varin, Emilie
• Lincet, Hubert
• Poulain, Laurent
• Icard, Philippe

Titel

Citrate induces apoptotic cell death: a promising way to treat gastric carcinoma?

Ist Teil von

• Anticancer research, 2011-03, Vol.31 (3), p.797-805

Ort / Verlag

Greece

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• Gastric carcinoma is frequent, particularly in China, and therapy is often inefficient. Because cancer cells are partly or mainly dependent on glycolysis to generate adenosine triphosphate ATP (Warburg effect) and/or to produce precursors (of lipid, nucleotides, etc.) for building new cells, any inhibition of glycolysis may slow down the cell proliferation and/or may kill cells. The antitumor effect of citrate, an anti-glycolytic agent inhibiting phosphofructokinase (PFK) was tested on two human gastric carcinoma cell lines. Cell viability and morphology were assessed after 24-72 h exposure to citrate (5, 10, 220 mM). Apoptosis was assessed by annexin V-FITC/PI staining and Western immunobloting. A 3-day continuous exposure to citrate led to near destruction of the cell population in both cell lines, apoptotic cell death occurred through the mitochondrial pathway in a dose- and time-dependent manner, associated with the reduction of the anti-apoptotic Mcl-1 protein in both lines. Citrate demonstrates strong cytotoxic activity against two gastric cancer lines, leading to an early diminution of expression of Mcl-1 and to massive apoptotic cell death involving the mitochondrial pathway.