Lycorine Inhibits the Proliferation of HL-60 Cell Line through Up-Regulation of p21.

In previous studies we found that lycorine had broad antitumor effects and tumor cells were more sensitive to lycorine than non-tumor cells. We also showed that the mitochondrial and cell death receptor pathways were involved in lycorine-induced apoptosis of HL-60 cells. To further explore the molecular mechanism by which lycorine inhibits cell proliferation, the gene chip technique was used to detect the difference of gene expression patterns between 5.0 μM lycorine-treated HL-60 cells and control. The chip included 494 genes associated with apoptosis and proliferation. This data set revealed a significant change of 91 genes in expression, with 79 being up-regulated and 12 down-regulated. In particular the tumor suppressor gene p21 was up-regulated 9.3 folds in the lycorine-treated group. Consistent with this finding, RT-PCR and Western blotting confirmed the up-regulation of p21 gene and its protein in HL-60 cells treated with 5.0 μM lycorine for 24 h. The levels of p21 protein and its downstream cell cycle molecules Cdc2, Cdk2 and cyclin E were assessed after HL-60 cells were incubated with 0, 1.25, 2.5 and 5.0 μM lycorine. The results showed that the expression of Cdc2, Cdk2 and cyclin E was down-regulated, while that of p21 was up-regulated. Thus, lycorine could induce cell cycle arrest by interfering with cell cycle signaling pathways through up-regulation of p21 and concomitant down-regulation of Cdc2, Cdk2 and cyclin E in HL-60 cells.