EFFECTS OF BAICALEIN AND ESCULETIN ON TRANSDUCTION SIGNALS AND GROWTH-FACTORS EXPRESSION IN T-LYMPHOID LEUKEMIA-CELLS

The possible mechanisms of antiproliferative effect of baicalein were studied in human T-lymphoid leukemia cells (CEM cells) and compared wi th those of esculetin. Baicalein, esculetin and related compounds, bai calin, wogonin, esculin and scoparone, inhibited CEM cell proliferatio n. Baicalein exhibited the greatest antiproliferative activity with an IC50 of 4.7 +/- 0.5 mu M and the maximal suppression of 91.5 +/- 1.4% in CEM cells. The protein tyrosine kinase activity in the CEM cells w as significantly reduced by baicalein (10(-6)-10(-4) M) and esculetin (10(-4) M). Baicalein exhibited a greater inhibitory activity on the p rotein tyrosine kinase than did esculetin (74.1 +/- 3.3% vs. 64.6 +/- 2.8% inhibition at 10(-4) M). On the other hand, the protein kinase C activity stimulated by phorbol-12-myristate 13-acetate was reduced by directly incubating with baicalein (10(-6)-10(-4) M) and esculetin (10 (-4) M). However, the inhibitory activities on protein kinase C did no t show a dose-dependency, The reverse transcription-polymerase chain r eaction analysis of platelet-derived growth factor-A (PDGF-A) and tran sforming growth factor-beta(1) (TGF-beta(1)) messenger RNA levels demo nstrates that baicalein and esculetin reduced the PDGF-A mRNA level, b ut less affected the TGF-beta(1) mRNA. Baicalein exhibited the greater reduction on the expression of PDGF-A mRNA than did esculetin. It is suggested that baicalein and esculetin may affect cell proliferation b y direct inhibiton of growth-related signal, protein tyrosine kinase, as well as reduction of mRNA expression of growth factor, platelet-der ived growth factor.