Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway.
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Coumarins
/ chemistry
Gene Expression Regulation
/ drug effects
Glioblastoma
/ drug therapy
Humans
Matrix Metalloproteinase 2
/ metabolism
Matrix Metalloproteinase 9
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
TOR Serine-Threonine Kinases
/ metabolism
Wnt Proteins
/ metabolism
beta Catenin
/ metabolism
Apoptosis
galbanic acid
glioblastoma
matrix metalloproteinase
migration
proliferation
Journal
Current molecular pharmacology
ISSN: 1874-4702
Titre abrégé: Curr Mol Pharmacol
Pays: United Arab Emirates
ID NLM: 101467997
Informations de publication
Date de publication:
2021
2021
Historique:
received:
31
12
2019
revised:
12
04
2020
accepted:
21
04
2020
pubmed:
13
5
2020
medline:
22
12
2021
entrez:
13
5
2020
Statut:
ppublish
Résumé
Glioblastoma is one of the most aggressive tumors of the central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies. The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells. The anti-proliferative activity of the compound was determined by the MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/β-catenin). Alteration in the level of protein Akt was determined by Western blotting. Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Moreover, it could decrease the migration capability of glioblastoma cells, which was accompanied by inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, β-catenin, and APC genes. In addition, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide. Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting the PI3K/Akt/mTOR pathway. This compound also reduced the migration capability of the cells by suppressing the activity and expression of MMPs.
Sections du résumé
BACKGROUND
Glioblastoma is one of the most aggressive tumors of the central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies.
OBJECTIVE
The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells.
METHODS
The anti-proliferative activity of the compound was determined by the MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/β-catenin). Alteration in the level of protein Akt was determined by Western blotting.
RESULTS
Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Moreover, it could decrease the migration capability of glioblastoma cells, which was accompanied by inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, β-catenin, and APC genes. In addition, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide.
CONCLUSION
Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting the PI3K/Akt/mTOR pathway. This compound also reduced the migration capability of the cells by suppressing the activity and expression of MMPs.
Identifiants
pubmed: 32394847
pii: CMP-EPUB-106549
doi: 10.2174/1874467213666200512075507
doi:
Substances chimiques
Antineoplastic Agents
0
Coumarins
0
Wnt Proteins
0
beta Catenin
0
galbanic acid
9OFS0HWC92
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Matrix Metalloproteinase 2
EC 3.4.24.24
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
79-87Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.