Our results show that chrysin exerts anticancer activity in glioblastoma cell lines possibly via the ERK/Nrf2 signaling pathway and indicate the potential application of chrysin as a natural sensitizer in chemotherapy.
To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373.
Inhibition experiments of JNK or ERK activities revealed that the ERK pathway strongly promotes cisplatin- and UV-induced apoptosis in these glioblastoma cells.
Kinase-deficient erbB proteins reduced epidermal growth factor (EGF)-induced tyrosine phosphorylation of endogenous Shc proteins and also reduced immediate and sustained EGF-induced ERK MAPK activities in human glioblastoma cells, although basal ERK MAPK activities were unaffected.
This is the first demonstration that migrating glioblastoma cells overexpress EphB2 in vitro and in vivo; glioma migration and invasion are promoted by activation of EphB2 or inhibited by blocking EphB2.
We studied EphB2 gain of function and loss of function in glioblastoma-derived stem-like neurospheres, whose in vivo growth pattern closely replicates human GBM.
In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated.
These data suggest that when overexpressed, EphA2 induces ERK activation through its tyrosine kinase activity, leading to S897 phosphorylation and promotion of glioblastoma cell proliferation.
In addition, we detected decreased nuclear localization of Nrf2 following combined treatment with ERK and PI3K inhibitors in three human glioblastoma cell lines and selected the cell line (U251) most sensitive to the inhibitors for further study.
Combined inhibition of DRD2 and Epidermal Growth Factor Receptor (EGFR) led to synergistic tumoricidal activity as well as ERK suppression in independent in vivo and in vitro glioblastoma models.
These novel outcomes suggested that knockdown of HDAC1 possibly suppressed the expression of phosphorylated AKT (p-AKT) and phosphorylated ERK (p-ERK) proteins, while overexpression of HDAC1 significantly increased p-AKT and p-ERK protein in glioblastoma cells.
Taken together, these results demonstrate that TAZ can promote proliferation and tumor formation in glioblastoma cells by potentiating the EGFR/AKT/ERK pathway, and provide the evidence for promising target for the treatment of glioblastoma.
Furthermore, our data identified MAPK-ERK-YAP signaling pathways as the primary molecular mechanisms by which TNFα modulated mitochondrial fission and glioblastoma apoptosis.
We found that knockdown of LKB1 significantly promoted <i>in vitro</i> proliferation, adhesion, invasion, and metformin-induced apoptosis, and simultaneously enhanced activation of ERK and mammalian-target of rapamycin (mTOR) signaling pathways in LKB1-compenent U87 and T98 glioblastoma cells.