Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 62, Issue 22, Pages 5061-5071Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf501047g
Keywords
glioblastoma multiforme; epithelial-to-mesenchymal transition; insulin-like growth factor-1; osthole; PI3K/Akt
Funding
- National Science Council of the Republic of China [NSC 101-2320-B-039-031-MY3]
- Department of Health (Taiwan)
- China Medical University Hospital Cancer Research Center of Excellence [DOH100-TD-C-111-005]
- China Medical University [CMU101-N2-03]
Ask authors/readers for more resources
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 GSK3 beta and recovered the GSK3 beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available