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Glaucocalyxin A induces G2/M cell cycle arrest and apoptosis through the PI3K/Akt pathway in human bladder cancer cells
- Source :
- International Journal of Biological Sciences
- Publication Year :
- 2018
- Publisher :
- Ivyspring International Publisher, 2018.
-
Abstract
- Glaucocalyxin A (GLA), a major component isolated from Rabdosia japonica, has been proven to show anti-bacterial and anti-tumor biological characteristics according to previous studies. However, its potential effect on bladder cancer remains unknown. The present research aims to investigate the underlying mechanism in treating bladder cancer in vivo and in vitro. Cell proliferation was analyzed by CCK-8 assay and colony formation. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of the cell cycle and apoptosis-related proteins were detected by western blotting and immunofluorescence staining. Meanwhile, the in vivo study was performed to evaluate the anti-tumor effect on a UMUC3 subcutaneous tumor of NOD/SCID mice model. GLA suppressed colony-formation ability, triggered G2/M arrest and promoted apoptosis of UMUC3 cells in a dose-dependent manner. Furthermore, western blotting showed that GLA downregulated the expressions of PI3K p85, p-Akt, Bcl-2, CDK1, Cyclin B1 whereas upregulated the levels of PTEN, Bax, Cleaved Caspase-3. In vivo, GLA at a dosage of 20 mg/kg significantly inhibited tumor growth compared with the control group by intraperitoneal injection. These results suggested that GLA-related G2/M arrest and apoptosis in UMUC3 cells were mediated by a suppressed PI3K/Akt signaling pathway, which regulated p21Waf1/Cip1 as well as intrinsic caspase cascade. Collectively, our observations could help to develop new drugs targeting the PI3K/Akt pathway for the treatment of bladder cancer.
- Subjects :
- 0301 basic medicine
Mice, SCID
Applied Microbiology and Biotechnology
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Mice, Inbred NOD
Cell Line, Tumor
Animals
Humans
PTEN
Molecular Biology
Ecology, Evolution, Behavior and Systematics
PI3K/AKT/mTOR pathway
Cell Proliferation
Cyclin-dependent kinase 1
biology
Cell growth
Chemistry
Akt/PKB signaling pathway
apoptosis
PTEN Phosphohydrolase
Cell Cycle Checkpoints
Cell Biology
Cell cycle
Glaucocalyxin A
G2 Phase Cell Cycle Checkpoints
030104 developmental biology
Urinary Bladder Neoplasms
PI3K/Akt pathway
Apoptosis
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
bladder cancer
cell cycle
Female
Diterpenes, Kaurane
Proto-Oncogene Proteins c-akt
Research Paper
Signal Transduction
Developmental Biology
Subjects
Details
- ISSN :
- 14492288
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Sciences
- Accession number :
- edsair.doi.dedup.....c5c626899d70779ff5453c8dd8e85e8f