EFFECTS OF PHORBOL ESTER ON CELL-GROWTH INHIBITION BY TRANSFORMING GROWTH FACTOR-BETA-1 IN HUMAN HEPATOMA-CELL LINES

The effects of phorbol ester on cell growth inhibition by transforming growth factor β 1 (TGF-β 1) in human hepatoma cell lines, Mahlavu and PLC/PRF/5, were investigated. TGF-β 1 (2.5 to 10 pM) alone could not inhibit the growth of Mahlavu cells, whereas in the presence of 12-O-tetradecanol phorbol 13-acetate (TPA) at 1 ng/ml, TGF-β 1 could suppress their growth in a dose-dependent manner. The growth of PLC/PRF/5 cells could be inhibited by addition of TGF-β 1 (2.5 to 10 pM) alone in a dose-dependent manner, and this action was not affected by TPA (1 ng/ml). The TGF-β 1 inhibition induced by TPA in Mahlavu cells could not be cancelled by addition of protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) (10 μM) or staurosporin (1 nM). Thus, TPA could induce TGF-β 1 inhibition of cell growth in Mahlavu cells which did not respond to TGF-β 1 alone, and activation of protein kinase C does not seem to be behind this TPA action. © 1990.