Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway.

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.

Shahcheraghi SH ，Lotfi M ，Soukhtanloo M ，Ghayour Mobarhan M ，Jaliani HZ ，Sadeghnia HR ，Ghorbani A ... -  《-》

Fucoxanthin Activates Apoptosis via Inhibition of PI3K/Akt/mTOR Pathway and Suppresses Invasion and Migration by Restriction of p38-MMP-2/9 Pathway in Human Glioblastoma Cells.

Liu Y ，Zheng J ，Zhang Y ，Wang Z ，Yang Y ，Bai M ，Dai Y ... -  《-》

[Kuwanon G inhibits growth, migration and invasion of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway].

Geng Z ，Yang J ，Niu M ，Liu X ，Shi J ，Liu Y ，Yao X ，Zhang Y ，Zhang X ，Hu J ... -  《-》

Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.

Zhang FY ，Hu Y ，Que ZY ，Wang P ，Liu YH ，Wang ZH ，Xue YX ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Curcumin potentiates the galbanic acid-induced anti-tumor effect in non-small cell lung cancer cells through inhibiting Akt/mTOR signaling pathway.

Galbanic acid (GBA), which is known as a sesquiterpene coumarin, has been reported to have various anti-tumor activities in different cells. Our study intended to investigate whether curcumin potentiates GBA-induced anti-tumor effect in non-small cell lung cancer cells. The combined effect of GBA and curcumin on cell viability was examined by MTT analysis. Cellular apoptosis was evaluated by flow cytometry analysis. Autophagy was defined by autophagosome observed by confocal microscopy after infected with GFP-LC3 adenovirus. In addition, the expression of marker proteins involved in cell apoptosis, autophagy, and Akt/mTOR signaling pathway were estimated by qRT-PCR and Western Blotting assay. 15 μM curcumin combined with 40 μM GBA could obtain better synergistic repressive efficacy on cell viability and notably induced cell apoptosis in A549 cells. Besides, curcumin in alliance with GBA could significantly inhibit cell migration and invasion. GFP-LC3 infection experiments elaborated that curcumin could potentiate GBA induced cell autophagy and restrain the phosphorylation of Akt/mTOR/P70s6k signaling pathway. What's more, the reaction of migration, apoptosis, and autophagy induced by curcumin and GBA treatment could be reversed by mTOR inhibitor rapamycin and AKT activator insulin.

Zhang Q ，Qiao H ，Wu D ，Lu H ，Liu L ，Sang X ，Li D ，Zhou Y ... -  《-》