Suppression of cell proliferation with induction of p21 by Cl(-) channel blockers in human leukemic cells.
The existence of Cl(-) channels in lymphocytes and neutrophils has been increasingly recognized, but the biological functions are not yet clear. We examined the effects of Cl(-) channel blockers on the cell proliferation and the cell cycle of human leukemic cell lines. The growth of leukemic cells was suppressed most efficiently by NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid), partially by 9-AC (9-anthracenecarboxylic acid) and tamoxifen, but not by stilbene compounds. NPPB increased the G0/G1 population and induced the expression of p21, one of the critical molecules for G1/S checkpoint. Antisense oligonucleotide for a NPPB-sensitive and stilbene-insensitive Cl(-) channel, ClC-2, sufficiently suppressed the ClC-2 protein synthesis, but did not affect the growth of leukemic cells. These findings suggest that NPPB-sensitive and stilbene-insensitive Cl(-) channels other than ClC-2 play important roles in cell cycles and cell proliferation of human leukemic cells.
Jiang
Baohong
B
Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi Osaka 570-8506, Japan.
Hattori
Naoki
N
Liu
Bing
B
Nakayama
Yasuhisa
Y
Kitagawa
Kaori
K
Inagaki
Chiyoko
C
D015152:Blotting, Northern; D015153:Blotting, Western; D000090007:CLC-2 Chloride Channels; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis*; D012313:RNA / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; D009579:Nitrobenzoates; D016376:Oligonucleotides, Antisense; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D012313:RNA; D015689:Oncogene Protein p21(ras)