Abstract
The inhibitory effect of a serine protease‐inhibiting tetra‐benzamidine derivative, TAPP‐Br, on the cell growth of 8 human colon carcinoma cell lines was examined and the mechanism of the inhibition was analyzed. TAPP‐Br inhibited the cell growth of all the colon carcinoma cell lines, and this effect was irreversible. The expression of mRNAs for nuclear oncogenes such as MYC, FOS and JUN was decreased by TAPP‐Br after treatment for 3 h and the effect continued for 48 h‐ mRNA expression of epidermal growth factor receptor, transforming growth factor‐β and type IV collagenase was suppressed at 48 h after the initiation of TAPP‐Br treatment, suggesting an indirect action of TAPP‐Br. TAPP‐Br decreased protein kinase C activity in the participate fraction, whereas it increased the enzyme activity in the soluble fraction. These findings overall suggest that the serine protease inhibitor, TAPP‐Br, might inhibit the cell growth of colon carcinoma cell lines through suppressing the expression of genes whose promoter contains a 12–0‐tetradecanoylphorbol‐13‐acetate‐responsive element or serum‐responsive element.
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