Abstract
Calcium ions have been implicated in the regulation or modulation of various cell functions. Calmodulin, a calcium modulator protein in the cell, may play an important role in cell proliferation. If the calcium ion level in the cell can be altered by the addition of calmodulin antagonist, the aberrant growth of glioma may be regulated. The authors, therefore, intended to examine the effect of a calmodulin antagonist W-7, on a cultured glioma cell strain (GA-1), which is chemically induced from a rat glioblast.
The results are as follows: 1) Inhibition dose of W-7 to 50% of normal cell growth, was 50 μM. W-5, a dechlorinated structural analog of W-7, which had a lower affinity to calmodulin showed no definite inhibition on GA-1 growth. 2) At lower concentrations of W-7 (12.5 μM) in the cultured medium, deoxyribonucleic acid (DNA) synthesis in GA-1 was not markedly inhibited, but ribonucleic acid (RNA) and protein syntheses were strongly suppressed. 3) At higher concentrations of W-7 (25 to 75 μM), DNA, RNA, and protein syntheses were all suppressed. 4) Calmodulin content of GA-1 cell (58.0±3.0 pg/mg soluble protein) was lowered to half of the control level by the addition of W-7 within 2 hours and was maintained afterwards at the lower level. These results indicate that administration of calmodulin antagonist W-7 may be effective for nonsurgical treatment of glioma.
