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Osthole Inhibits Insulin-like Growth Factor-1-Induced Epithelial to Mesenchymal Transition via the Inhibition of PI3K/Akt Signaling Pathway in Human Brain Cancer Cells
- Source :
- Journal of Agricultural and Food Chemistry. 62:5061-5071
- Publication Year :
- 2014
- Publisher :
- American Chemical Society (ACS), 2014.
-
Abstract
- Glioblastoma multiforme (GBM) is one of the most lethal types of tumors and highly metastatic and invasive. The epithelial-to-mesenchymal transition (EMT) is the crucial step for cancer cells to initiate the metastasis and could be induced by many growth factors. In this study, we found that GBM8401 cells were converted to fibroblastic phenotype and the space between the cells became expanded in response to insulin-like growth factor-1 (IGF-1) treatment. Epithelial markers were downregulated and mesenchymal markers were upregulated simultaneously after IGF-1 treatment. Our results illustrate that IGF-1 was able to induce EMT in GBM8401 cells. Osthole would reverse IGF-1-induced morphological changes, upregulated the expression of epithelial markers, and downregulated the expression of mesenchymal markers. Moreover, wound-healing assay also showed that osthole could inhibit IGF-1-induced migration of GBM8401 cells. By using dual-luciferase reporter assay and real-time PCR, we demonstrated that osthole inhibited IGF-1-induced EMT at the transcriptional level. Our study found that osthole decreased the phosphorylation of Akt and GSK3β and recovered the GSK3β bioactivity in inhibiting EMT transcription factor Snail and Twist expression. These results showed that osthole inhibited IGF-1-induced EMT by blocking PI3K/Akt pathway. We hope that osthole can be used in anticancer therapy and be a new therapeutic medicine for GBM in the future.
- Subjects :
- Epithelial-Mesenchymal Transition
medicine.medical_treatment
Biology
Cnidium
Metastasis
Phosphatidylinositol 3-Kinases
Insulin-like growth factor
Downregulation and upregulation
Coumarins
Cell Line, Tumor
medicine
Humans
Epithelial–mesenchymal transition
Insulin-Like Growth Factor I
Phosphorylation
Reporter gene
Brain Neoplasms
Mesenchymal stem cell
General Chemistry
medicine.disease
Cell culture
Cancer cell
Immunology
Cancer research
Glioblastoma
General Agricultural and Biological Sciences
Proto-Oncogene Proteins c-akt
Drugs, Chinese Herbal
Signal Transduction
Subjects
Details
- ISSN :
- 15205118 and 00218561
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Journal of Agricultural and Food Chemistry
- Accession number :
- edsair.doi.dedup.....50fec9a84684aca70c43a336937f0952