Back to Search
Start Over
Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways
- Source :
- International Journal of Oncology.
- Publication Year :
- 2011
- Publisher :
- Spandidos Publications, 2011.
-
Abstract
- Wogonin (5,7-dihydroxy-8-methoxyflavone) is a flavone constituent of Scutellaria baicalensis with various beneficial biological activities and it has been shown to have tumor therapeutic potential in vitro and in vivo. The purpose of this study was to investigate the effects of wogonin in a human osteosarcoma cell line (U-2 OS). Results showed that a dose- and time-dependent reduction occurred in cell viability after exposure to wogonin in U-2 OS cells. Increasing the levels of reactive oxygen species (ROS) and Ca 2+ but decreasing the levels of mitochondrial membrane potential (∆Ψm) were examined in wogonin-treated U-2 OS cells. Flow cytometric assay indicated that wogonin induced sub-G1 phase (apoptosis) and increased caspase-3 activity in examined cells. Wogonin-induced apoptosis in U-2 OS cells was also confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining. Also, results from Western blotting indicated that wogonin increased the levels of Bad, Bax, cytochrome c, cleaved caspase-9, cleaved caspase-3, AIF, Endo G, Fas/CD95, caspase-8, GADD153, GRP78, ATF-6α, calpain 1, calpain 2 and caspase-4 then leading to cell apoptosis. In conclusion, wogonin induced ROS production and intracellular Ca 2+ , and altered the levels of anti- (Bcl-2) and pro- (Bad and Bax) apoptotic proteins. Wogonin-induced apoptosis in U-2 OS cells was through the activation of caspase-3. In conclusion, these are the first findings to show wogonin-induced cytotoxic effects through induction of apoptotic cell death and ER stress in U-2 OS cells. The potent in vitro antitumor activities suggest that wogonin could be developed for the treatment of human osteosarcoma in the future.
- Subjects :
- Cancer Research
Programmed cell death
Cell Survival
Intracellular Space
Apoptosis
Caspase 3
Endoplasmic Reticulum
Models, Biological
chemistry.chemical_compound
Wogonin
Cell Line, Tumor
Humans
DAPI
Endoplasmic Reticulum Chaperone BiP
Membrane Potential, Mitochondrial
Osteosarcoma
biology
Calpain
Fas receptor
biology.organism_classification
Mitochondria
Oncology
Biochemistry
chemistry
Flavanones
biology.protein
Cancer research
Scutellaria baicalensis
Calcium
Reactive Oxygen Species
Drugs, Chinese Herbal
Signal Transduction
Subjects
Details
- ISSN :
- 17912423 and 10196439
- Database :
- OpenAIRE
- Journal :
- International Journal of Oncology
- Accession number :
- edsair.doi.dedup.....196d486748ccee3c25e719b9d3dbf986