Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823.

Abstract

AIM:

To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.

METHODS:

Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR.

RESULTS:

After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells was exposed to GA for 24, 48 and 72 h, the IC(50) value were 1.02+/-0.05, 1.41+/-0.20 and 1.14+/-0.19 micromol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by Annexin-V/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 micromol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR.

CONCLUSION:

The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of the expression of apoptosis-regulated gene bax. The result was also confirmed in vivo.

• Authors: Wei Liu, Qing-Long Guo, Qi-Dong You, Li Zhao, Hong-Yan Gu, Sheng-Tao Yuan
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 11 Issue 24 Pg. 3655-9 (Jun 28 2005) ISSN: 1007-9327 [Print] United States
• PMID: 15968715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Xanthones
• gambogic acid

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Humans
• Medicine, Chinese Traditional
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Stomach Neoplasms (drug therapy, pathology)
• Xanthones (pharmacology)
• Xenograft Model Antitumor Assays