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Costunolide Induces Apoptosis through Generation of ROS and Activation of P53 in Human Esophageal Cancer Eca-109 Cells.
- Source :
-
Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2016 Sep; Vol. 30 (9), pp. 462-9. Date of Electronic Publication: 2016 Apr 14. - Publication Year :
- 2016
-
Abstract
- Costunolide is a sesquiterpene lactone, which possesses potent anti-cancer properties. However, there is little report about its effects on esophageal cancer. In our study, we investigated the effects of costunolide on the cell viability, cell cycle, and apoptosis in human esophageal cancer Eca-109 cells. It was found that costunolide inhibited the growth of Eca-109 cells in a dose-dependent manner, which was associated with the loss of mitochondrial membrane potential (Δψm ) and the production of ROS. Costunolide induced apoptosis of Eca-109 cells as well as cell cycle arrest in G1/S phase by upregulation of P53 and P21. Costunolide triggered apoptosis in esophageal cancer cells via the upregulation of Bax, downregulation of Bcl-2, and significant activation of caspase-3 and poly ADP-ribose polymerase. These effects were markedly abrogated when cells were pretreated with N-acetylcysteine, a specific reactive oxygen specie inhibitor. These results suggest that costunolide is a potential candidate for the treatment of esophageal cancer.<br /> (© 2016 Wiley Periodicals, Inc.)
- Subjects :
- Acetylcysteine pharmacology
Apoptosis genetics
Caspase 3 genetics
Caspase 3 metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Cyclin-Dependent Kinase Inhibitor p21 agonists
Cyclin-Dependent Kinase Inhibitor p21 genetics
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Dose-Response Relationship, Drug
Epithelial Cells metabolism
Epithelial Cells pathology
Esophagus drug effects
Esophagus metabolism
Esophagus pathology
Free Radical Scavengers pharmacology
Gene Expression Regulation
Humans
Membrane Potential, Mitochondrial drug effects
Mitochondria drug effects
Poly(ADP-ribose) Polymerases genetics
Poly(ADP-ribose) Polymerases metabolism
Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Reactive Oxygen Species agonists
Reactive Oxygen Species metabolism
Signal Transduction
Tumor Suppressor Protein p53 agonists
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
bcl-2-Associated X Protein agonists
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Epithelial Cells drug effects
G1 Phase Cell Cycle Checkpoints drug effects
Sesquiterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1099-0461
- Volume :
- 30
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of biochemical and molecular toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 27078502
- Full Text :
- https://doi.org/10.1002/jbt.21810