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Alpha-tomatine inactivates PI3K/Akt and ERK signaling pathways in human lung adenocarcinoma A549 cells: effect on metastasis
- Source :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 47(8)
- Publication Year :
- 2009
-
Abstract
- This study first investigates the anti-metastatic effect of alpha-tomatine in the human lung adenocarcinoma cell line: A549. In this study, we first noted alpha-tomatine inhibited A549 cells invasion and migration by wound-healing assay and Boyden chamber assay. The data also showed alpha-tomatine could inhibit phosphorylation of Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2), which is involved in the up-regulating matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) or urokinase-type plasminogen activator (u-PA), whereas it did not affect phosphorylation of c-Jun N-terminal kinase (JNK) and p38. Next, alpha-tomatine significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, treating A549 cells with alpha-tomatine also leads to a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1). Further, the treatment of inhibitors specific for PI3K (Wortmannin) or ERK (U0126) to A549 cells could cause reduced activities of MMP-2, MMP-9, and u-PA. These results showed alpha-tomatine could inhibit the metastatic ability of A549 cells by reducing MMP-2, MMP-9, and u-PA activities through suppressing phosphoinositide 3-kinase/Akt (PI3K/Akt) or ERK1/2 signaling pathway and inhibition NF-kappaB or AP-1 binding activities. These findings proved alpha-tomatine might be an anti-metastatic agent against human lung adenocarcinoma.
- Subjects :
- MAPK/ERK pathway
Tetrazolium Salts
Electrophoretic Mobility Shift Assay
Biology
Toxicology
Wortmannin
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
Tomatine
Cell Movement
Cell Line, Tumor
Humans
Neoplasm Invasiveness
Enzyme Inhibitors
Neoplasm Metastasis
Coloring Agents
Extracellular Signal-Regulated MAP Kinases
Protein kinase B
PI3K/AKT/mTOR pathway
A549 cell
Cell Nucleus
Wound Healing
Kinase
General Medicine
Urokinase-Type Plasminogen Activator
Oncogene Protein v-akt
Thiazoles
chemistry
Carbohydrate Sequence
Matrix Metalloproteinase 9
Cancer research
Phosphorylation
Matrix Metalloproteinase 2
Signal transduction
Neoplasm Transplantation
Food Science
Signal Transduction
Subjects
Details
- ISSN :
- 18736351
- Volume :
- 47
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Accession number :
- edsair.doi.dedup.....0dd716363f70c2841b3c4f3fc052bc85