Bufalin Inhibits NCI-H460 Human Lung Cancer Cell Metastasis In Vitro by Inhibiting MAPKs, MMPs, and NF-κB Pathways.
Am J Chin Med
; 43(6): 1247-64, 2015.
Article
in En
| MEDLINE
| ID: mdl-26446205
ABSTRACT
Bufalin, a component of Chan Su (a traditional Chinese medicine), has been known to have antitumor effects for thousands of years. In this study, we investigated its anti-metastasis effects on NCI-H460 lung cancer cells. Under sub-lethal concentrations (from 25 up to 100 nM), bufalin significantly inhibits the invasion and migration nature of NCI-H460 cells that were measured by Matrigel Cell Migration Assay and Invasion System. Bufalin also suppressed the enzymatic activity of matrix metalloproteinase (MMP)-9, which was examined by gelatin zymography methods. Western blotting revealed that bufalin depressed several key metastasis-related proteins, such as NF-κB, MMP-2, MMP-9, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3-K), phosphorylated Akt, growth factor receptor-bound protein 2 (GRB2), phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated p38, and phosphorylated c-Jun NH2-terminal kinase (JNK). As evidenced by immunostaining and the electrophoretic mobility shift assay (EMSA), bufalin induced not only a decreased cytoplasmic NF-κB production, but also decreased its nuclear translocation. Several metastasis-related genes, including Rho-associated (Rho A), coiled-coil-containing protein kinase 1 (ROCK1), and focal adhesion kinase (FAK), were down-regulated after bufalin treatment. In conclusion, bufalin is effective in inhibiting the metastatic nature of NCI-H460 cells in low, sub-lethal concentrations. Such an effect involves many mechanisms including MMPs, mitogen-activated protein kinases (MAPKs) and NF-κB systems. Bufalin has a potential to evolve into an anti-metastasis drug for human lung cancer in the future.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bufanolides
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NF-kappa B
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Extracellular Signal-Regulated MAP Kinases
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Lung Neoplasms
Limits:
Humans
Language:
En
Journal:
Am J Chin Med
Year:
2015
Document type:
Article
Affiliation country:
Taiwan
Publication country:
SG
/
SINGAPORE
/
SINGAPUR
/
SINGAPURA