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Inhibition of glioblastoma growth and angiogenesis by gambogic acid: An in vitro and in vivo study
- Source :
- Biochemical Pharmacology. 75:1083-1092
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Gambogic acid (GA) is the major active ingredient of gamboge, a brownish to orange resin exuded from Garcinia hanburryi tree in Southeast Asia. The present study aims to demonstrate that gambogic acid (GA) has potent anticancer activity for glioblastoma by in vitro and in vivo study. Rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). To reveal an involvement of the intrinsic mitochondrial pathway of apoptosis, the mitochondrial membrane potential and the western blot evaluation of Bax, Bcl-2, Caspase-3, caspase-9 and cytochrome c released from mitochondria were performed. Angiogenesis was detected by CD31 immunochemical study. The results showed that the uptake of GA by rBMEC was time-dependent, which indicated that it could pass BBB and represent a possible new target in glioma therapy. GA could cause apoptosis of rat C6 glioma cells in vitro in a concentration-dependent manner by triggering the intrinsic mitochondrial pathway of apoptosis. In vivo study also revealed that i.v. injection of GA once a day for two weeks could significantly reduce tumor volumes by antiangiogenesis and apoptotic induction of glioma cells. Collectively, the current data indicated that GA may be of potential use in treatment of glioblastoma by apoptotic induction and antiangiogenic effects.
- Subjects :
- Programmed cell death
Cell Survival
Angiogenesis
Xanthones
Angiogenesis Inhibitors
Apoptosis
Mitochondrion
Biology
Biochemistry
Rats, Sprague-Dawley
chemistry.chemical_compound
In vivo
Cell Line, Tumor
Glioma
medicine
Animals
Cells, Cultured
Cell Proliferation
Membrane Potential, Mitochondrial
Pharmacology
Cytochromes c
medicine.disease
In vitro
Rats
Tumor Burden
chemistry
Cancer research
Gambogic acid
Apoptosis Regulatory Proteins
Glioblastoma
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....33240a22a7dc89ed6bbe1e53e2b222b9