UNLABELLED: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
UNLABELLED: 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 triphosphateATP (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 humangastric carcinoma cell lines. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: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.
Authors: S M El Sayed; R M Abou El-Magd; Y Shishido; S P Chung; T H Diem; T Sakai; H Watanabe; S Kagami; K Fukui Journal: J Bioenerg Biomembr Date: 2012-02-09 Impact factor: 2.945
Authors: S M El Sayed; R M Abou El-Magd; Y Shishido; K Yorita; S P Chung; D H Tran; T Sakai; H Watanabe; S Kagami; K Fukui Journal: J Bioenerg Biomembr Date: 2012-07-17 Impact factor: 2.945