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Evodiamine induces apoptosis and inhibits metastasis in MDA-MB-231 human breast cancer cells in vitro and in vivo
- Source :
- Oncology Reports. 30:685-694
- Publication Year :
- 2013
- Publisher :
- Spandidos Publications, 2013.
-
Abstract
- Breast cancer remains the leading cause of cancer-related deaths among women. Owing to high efficiency and low toxic effects, further exploration of natural compounds from Chinese herbal medicine may be an efficient approach for breast cancer drug discovery. In this study, we investigated the effects of evodiamine on the growth and metastasis of MDA-MB-231 human breast cancer cells in vitro and in vivo. In vitro, evodiamine inhibited cell migration and invasion abilities through downregulation of MMP-9, urokinase-type plasminogen activator (uPA) and uPAR expression. Evodiamine-induced G0/G1 arrest and apoptosis were associated with a decrease in Bcl-2, cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression and an increase in Bax and p27Kip1 expression. Moreover, evodiamine regulated p-ERK and p-p38 MAPK expression. Evodiamine-induced apoptosis was enhanced by its combination with the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580. Evodiamine-inhibited metastasis was partly blocked by combination with PD98059 or SB203580. In vivo, the administration of evodiamine (10 mg/kg) significantly reduced tumor growth and pulmonary metastasis. These results demonstrate that evodiamine possesses antitumor activities via inhibition of cell migration and invasion, arrest of the cell cycle and induction of cell apoptosis in MDA-MB-231 cells.
- Subjects :
- MAPK/ERK pathway
Cancer Research
Down-Regulation
Mice, Nude
Apoptosis
Breast Neoplasms
Biology
Resting Phase, Cell Cycle
p38 Mitogen-Activated Protein Kinases
Receptors, Urokinase Plasminogen Activator
Metastasis
Mice
chemistry.chemical_compound
Cyclin D1
Cell Movement
Evodiamine
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Extracellular Signal-Regulated MAP Kinases
Cell Proliferation
bcl-2-Associated X Protein
Mice, Inbred BALB C
G1 Phase
Cell Cycle Checkpoints
Cyclin-Dependent Kinase 6
General Medicine
Cell cycle
medicine.disease
Urokinase-Type Plasminogen Activator
Urokinase receptor
Matrix Metalloproteinase 9
Proto-Oncogene Proteins c-bcl-2
Oncology
chemistry
Cancer cell
Quinazolines
Cancer research
biology.protein
Female
Cyclin-dependent kinase 6
Cyclin-Dependent Kinase Inhibitor p27
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....fbba810117b93d3e12cd53f204fadeaf