Inhibition of proliferation of MCF-7 breast cancer cells by a blocker of Ca(2+)-permeable channel.
In MCF-7 breast cancer cells, insulin-like growth factor-1 (IGF-1) increased the calcium-permeability of the cells by activating a voltage-independent calcium-permeable channel. IGF-1 also induced oscillatory elevation of cytoplasmic free calcium concentration in these cells. An anti-allergic compound, tranilast, reduced the calcium-permeability augmented by IGF-1 in a dose-dependent manner and blocked the oscillatory elevation of cytoplasmic free calcium concentration. Tranilast did not affect early intracellular signals activated by IGF-1, including receptor autophosphorylation, activations of Ras, mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Tranilast inhibited increases in [3H]-thymidine incorporation, DNA content and cell number induced by IGF-1. The ID50 for [3H]-thymidine incorporation and DNA content were about 10 microM. The inhibitory effect of tranilast was reversible, and cell viability was not affected. Treatment with tranilast increased the number of cells in the G1 phase suggesting that this compound induced G1 arrest. Tranilast also reduced the phosphorylation of the retinoblastoma protein. These results indicate that tranilast inhibits the IGF-1-induced cell growth in MCF-7 cells by blocking calcium entry.
Nie
L
L
Department of Cell Biology, Gunma University, Maebashi, Japan.
Oishi
Y
Y
Doi
I
I
Shibata
H
H
Kojima
I
I
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D053938:DNA Fragmentation; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004273:DNA, Neoplasm; D016160:Retinoblastoma Protein; D062367:ortho-Aminobenzoates; D007334:Insulin-Like Growth Factor I; C012293:tranilast; D002118:Calcium