Effect of pseudolaric acid B on gastric cancer cells: inhibition of proliferation and induction of apoptosis.

Abstract

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 G(2)/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 G(2)/M phase arrest. These findings are consistent with the possibility that G(2)/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.

• Authors: Ke-Shen Li, Xue-Feng Gu, Ping Li, Yong Zhang, Ya-Shuang Zhao, Zhen-Jiang Yao, Nai-Qiang Qu, Bin-You Wang
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 11 Issue 48 Pg. 7555-9 (Dec 28 2005) ISSN: 1007-9327 [Print] United States
• PMID: 16437677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Drugs, Chinese Herbal
• Proto-Oncogene Proteins c-bcl-2
• pseudolaric acid B
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• Caspase 3
• Caspases

Topics

• Apoptosis (drug effects)
• Caspase 3
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Fragmentation (drug effects)
• Diterpenes (pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• Flow Cytometry
• Humans
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• Stomach Neoplasms (drug therapy, pathology)