Suppressive effect of ethyl acetate extract of Paecilomyces japonica on cell cycle progression of human acute leukemia Jurkat T cell clone overexpressing Bcl-2

To understand antitumor activity of an edible mushroom Paecilomyces japonica, we have investigated its effect on the cell cycle. When Jurkat T cells transfected with vector (JT/Neo) or Bcl-2 gene (JT/Bcl-2) were treated with the ethyl acetate extract (4-6 μg/ml) of P. japonica for 40 h, JT/Neo cells underwent apoptosis with no detectable G₁-arrest, whereas JT/Bcl-2 cells that failed to induce apoptosis accumulated at the G₁ along with reduction of hyperphosphorylated Rb. The cdk4, cyclin E and A, required for the G₁-cdks that phosphorylate Rb, were markedly downregulated in JT/Bcl-2 cells, and the G₁-cdk inhibitor p27^Kip1 was significantly upregulated. GC-MS analysis identified a component structurally similar to diacetoxyscirpenol as the effective ingredient contributing to the G₁-arrest. These results demonstrate that P. japonica can arrest the cell cycle of JT/Bcl-2 cells at the G₁ by suppressing phosphorylation of Rb through downregulation of the activity of G₁-cdks, and thus potentiates apoptotic cell death.