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Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells
- Source :
- Toxicology. 260(1-3)
- Publication Year :
- 2009
-
Abstract
- It is reported that gambogic acid (GA), the main active compound of gamboge which is a dry resin extracted from Garcinia hanburyi tree, has potent antitumor activity both in vivo and in vitro. Activation of mitochondrial apoptotic pathway in cancer cells is one effective therapy for cancer treatment. In the present study, we focus on the effect of GA on induction of reactive oxygen species (ROS) accumulation and triggering the mitochondrial signaling pathway in human hepatoma SMMC-7721 cells. The results indicated that GA induced ROS accumulation and collapse of mitochondrial membrane potential in SMMC-7721 cells in a concentration-dependent manner and subsequently induced that release of Cytochrome c and apoptosis-inducing factor from mitochondria to cytosol, which inhibited ATP generation and induced apoptosis in the cells. Moreover, GA elevated the phosphorylation of c-Jun-N-terminal protein kinase (JNK) and p38, which was the downstream effect of ROS accumulation. Furthermore, N-acetylcysteine, a ROS production inhibitor, partly reversed the activation of JNK and p38 and the induction of apoptosis in GA-treated cells. Collectively, our study demonstrated that accumulation of ROS played an important role in GA-induced mitochondrial signaling pathway, which provided further theoretical support for the application of GA as a promising anticancer agent.
- Subjects :
- Programmed cell death
Cell Survival
Xanthones
Blotting, Western
Apoptosis
Mitochondria, Liver
Mitochondrion
Toxicology
medicine.disease_cause
p38 Mitogen-Activated Protein Kinases
chemistry.chemical_compound
Adenosine Triphosphate
Cell Line, Tumor
medicine
Humans
chemistry.chemical_classification
Membrane Potential, Mitochondrial
Reactive oxygen species
Microscopy, Confocal
biology
Cytochrome c
Liver Neoplasms
JNK Mitogen-Activated Protein Kinases
Apoptosis Inducing Factor
Cytochromes c
Free Radical Scavengers
Flow Cytometry
Antineoplastic Agents, Phytogenic
Glutathione
Cell biology
Acetylcysteine
chemistry
Biochemistry
Cancer cell
biology.protein
Gambogic acid
Reactive Oxygen Species
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 18793185
- Volume :
- 260
- Issue :
- 1-3
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....235061e1a8cb63fb753d7ca198e07138