Differential apoptotic induction of gambogic acid, a novel anticancer natural product, on hepatoma cells and normal hepatocytes

Abstract Gambogic acid (GA) is the major active ingredient of gamboge, a brownish resin exuded from Garcinia hanburryi tree in Southeast Asia. In this study, we compared the different apoptotic induction of GA on human normal embryon hepatic L02 cells and human hepatoma SMMC-7721 cells by detecting...

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Bibliographic Details
Published in:Cancer letters 2007-10, Vol.256 (2), p.259-266
Main Authors: Yang, Yong, Yang, Lan, You, Qi-Dong, Nie, Fei-Fei, Gu, Hong-Yan, Zhao, Li, Wang, Xiao-Tang, Guo, Qing-Long
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Phytogenic - pharmacokinetics
Antineoplastic Agents, Phytogenic - pharmacology
Antineoplastic Agents, Phytogenic - therapeutic use
Apoptosis
Apoptosis - drug effects
Bax
Bcl-2
bcl-2-Associated X Protein - metabolism
Blotting, Western
Cancer
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Caspase 3 - metabolism
Caspase-3
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Shape - drug effects
Cells, Cultured
Cold
Dose-Response Relationship, Drug
Female
Gambogic acid
Garcinia
Hematology, Oncology and Palliative Medicine
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - pathology
Humans
Laboratory animals
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Proteins
Proto-Oncogene Proteins c-bcl-2 - metabolism
R&D
Rats
Rats, Sprague-Dawley
Research & development
Retention
Rodents
Statistical methods
Xanthones - pharmacokinetics
Xanthones - pharmacology
Xanthones - therapeutic use
Xenograft Model Antitumor Assays
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Summary:Abstract Gambogic acid (GA) is the major active ingredient of gamboge, a brownish resin exuded from Garcinia hanburryi tree in Southeast Asia. In this study, we compared the different apoptotic induction of GA on human normal embryon hepatic L02 cells and human hepatoma SMMC-7721 cells by detecting growth inhibition, observing morphological changes, and the expressions of the relative apoptotic proteins (Bax, Bcl-2 and caspase-3). The results indicated that GA could selectively induce apoptosis of SMMC-7721 cells, while had relatively less effect on L02 cells. To illustrate the distinct selective antitumor mechanism of GA, we further study its distribution in cultured cells and in tumor-bearing mice. The results indicated that SMMC-7721 cells have higher GA binding activity than L02 cells. The retention time of GA in grafted tumor was longer than in liver, renal and other organs. Collectively, the selective anticancer activity of GA could be due to its significant apoptotic inducing effects as well as its higher distribution and longer retention time in tumor cells compared to the normal cells. So GA might be a kind of highly effective anticancer drug candidate with low toxicity to normal tissue.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2007.06.014