Intracellular chloride regulates the G1/S cell cycle progression in gastric cancer cells

Figure 1 Na⁺/K⁺/2Cl^- cotransporter controls the intracellular chloride concentration via uptake of Cl^- into the intracellular space. Furosemide, a blocker of Na⁺/K⁺/2Cl^- cotransporter, delays the G₁-S phase progression by decreasing the intracellular chloride concentration ([Cl^-]_i) in gastric cancer cells.

Figure 2 Experimental method for regulation of the intracellular chloride concentration of cultured cells. The intracellular chloride concentration ([Cl^-]_i) of gastric cancer cells is decreased by the culture in the low Cl^- medium, which were prepared by substituting, respectively, NaCl and KCl with NaNO₃ and KNO₃.

Figure 3 Roles of the intracellular chloride concentration in cell cycle progression of gastric cancer cells. The intracellular chloride concentration ([Cl^-]_i) affects the cell proliferation via activation of p38 and/or JNK cascades through upregulation of the p21. The decrease of the [Cl^-]_i causes the G₀/G₁ phase arrest by diminishing expression of CDK2 and phosphorylated Rb due to an increase in expression of p21.