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

Wei Liu

Qing Guo

Qi You

Li Zhao

Hong Gu

Sheng Yuan

Wei Liu, Qing-Long Guo, Li Zhao, Hong-Yan Gu, Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Qi-Dong You, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Sheng-Tao Yuan, the National Laboratory of New Drug Screen, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Author contributions: All authors contributed equally to the work.

Correspondence to: Professor Qing-Long Guo, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, Jiangsu Province, China. moc.liamtoh@ouggnolgniq

Telephone: +86-25-83271055 Fax:+86-25-3271055

Wei Liu, Qing-Long Guo, Li Zhao, Hong-Yan Gu, Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Qi-Dong You, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Sheng-Tao Yuan, the National Laboratory of New Drug Screen, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China

Author contributions: All authors contributed equally to the work.

Correspondence to: Professor Qing-Long Guo, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, Jiangsu Province, China. moc.liamtoh@ouggnolgniq

Telephone: +86-25-83271055 Fax:+86-25-3271055

Received 2004 Nov 8; Revised 2004 Nov 9; Accepted 2004 Dec 3.

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 were exposed to GA for 24, 48 and 72 h, the IC₅₀ value was 1.02±0.05, 1.41±0.20 and 1.14±0.19 μmol/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 μmol/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.

Keywords: Gambogic acid, Apoptosis, bcl-2, bax

Abstract

Footnotes

Supported by The National High Technology Research and Development Program Foundation of China, 863 Program, No. 2002AA2Z3112, and the Ministry of Education Science and Technology Program, No. 104099, affiliated to National Natural Science Foundation of China, No. 30472044

Co-first-authors: Wei Liu and Qing-Long Guo

Co-correspondents: Qing-Long Guo

Science Editor Guo SY Language Editor Elsevier HK

Footnotes

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