Published online Dec 28, 2005. doi: 10.3748/wjg.v11.i48.7555
Revised: July 5, 2005
Accepted: July 12, 2005
Published online: December 28, 2005
AIM: To examine the effect of pseudolaric acid B on the growth of human gastric cancer cell line, AGS, and its possible mechanism of action.
METHODS: Growth inhibition by pseudolaric acid B was analyzed using MTT assay. Apoptotic cells were detected using Hoechst 33258 staining, and confirmed by DNA fragmentation analysis. Western blot was used to detect the expression of apoptosis-regulated gene Bcl-2, caspase 3, and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1).
RESULTS: Pseudolaric acid B inhibited the growth of AGS cells in a time- and dose-dependent manner by arresting the cells at G2/M phase, which was accompanied with a decrease in the levels of cdc2. AGS cells treated with pseudolaric acid B showed typical characteristics of apoptosis including chromatin condensation and DNA fragmentation. Moreover, treatment of AGS cells with pseudolaric acid B was also associated with decreased levels of the anti-apoptotic protein Bcl-2, activation of caspase-3, and proteolytic cleavage of PARP-1.
CONCLUSION: Pseudolaric acid B can dramatically suppress the AGS cell growth by inducing apoptosis after G2/M phase arrest. These findings are consistent with the possibility that G2/M phase arrest is mediated by the down-regulation of cdc2 levels. The data also suggest that pseudolaric acid B can trigger apoptosis by decreasing Bcl-2 levels and activating caspase-3 protease.