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 with those of esculetin. Baicalein, esculetin and related compounds, baicalein, wogonin, esculin and scoparone, inhibited CEM cell proliferation. Baicalein exhibited the greatest antiproliferative activity with an IC50 of 4.7 +/- 0.5 microM and the maximal suppression of 91.5 +/- 1.4% in CEM cells. The protein tyrosine kinase activity in the CEM cells was significantly reduced by baicalein (10(-6)-10(-4) M) and esculetin (10(-4) M). Baicalein exhibited a greater inhibitory activity on the protein 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 not show a dose-dependency. The reverse transcription-polymerase chain reaction analysis of platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta 1 (TGF-beta 1) messenger RNA levels demonstrates that baicalein and esculetin reduced the PDGF-A mRNA level, but 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 by direct inhibition of growth-related signal, protein tyrosine kinase, as well as reduction of mRNA expression of growth factor, platelet-derived growth factor.