Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells.
The aim of the present study is to investigate whether the chloride affects cell growth and cell-cycle progression of cancer cells. In human gastric cancer MKN28 cells, the culture in the Cl(-)-replaced medium (replacement of Cl(-) by NO(3)(-)) decreased the intracellular chloride concentration ([Cl(-)](i)) and inhibited cell growth. The inhibition of cell growth was due to cell-cycle arrest at the G(0)/G(1) phase caused by diminution of CDK2 and phosphorylated Rb. The culture of cells in the Cl(-)-replaced medium significantly increased expressions of p21 mRNA and protein without any effects on p53. These observations indicate that chloride ions play important roles in cell-cycle progression by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells, leading to a novel, unique therapeutic strategy for gastric cancer treatment via control of [Cl(-)](i).
Miyazaki
Hiroaki
H
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Shiozaki
Atsushi
A
Niisato
Naomi
N
Ohsawa
Rumi
R
Itoi
Hirosumi
H
Ueda
Yuji
Y
Otsuji
Eigo
E
Yamagishi
Hisakazu
H
Iwasaki
Yoshinobu
Y
Nakano
Takashi
T
Nakahari
Takashi
T
Marunaka
Yoshinori
Y
D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002713:Chlorine / Q000008:administration & dosage*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007477:Ions; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007477:Ions; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002713:Chlorine