Glioblastoma is one of the most lethal and prevalent malignant human
brain tumors, with aggressive proliferation and highly invasive properties. There is still no effective cure for patients with
glioblastoma.
Honokiol, derived from Magnolia officinalis, can cross the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), making it a strong candidate for an effective
drug for the treatment of
brain tumors, including
glioblastoma. In our previous study, we demonstrated that
honokiol effectively induced apoptotic cell death in
glioblastoma.
Metastasis poses the largest problem to
cancer treatment and is the primary cause of death in
cancer patients. Thus, in this study, we investigated the effect of
honokiol on the cell invasion process of U87MG human
glioblastoma cells through brain microvascular endothelial cells (BMECs) and its possible mechanisms.
Honokiol dose-dependently inhibited TNF-α-induced
VCAM-1 expression in BMECs and adhesion of U87MG to BMECs. Moreover,
honokiol effectively blocked U87MG invasion through BMEC-
Matrigel-coated transwell membranes. Increased phosphorylation of
VE-cadherin and membrane permeability by TNF-α were suppressed by
honokiol in BMECs. Furthermore, we investigated the effect of
honokiol on the epithelial-mesenchymal transition (EMT) in U87MG cells.
Honokiol reduced the expression levels of Snail,
N-cadherin and β-
catenin, which are mesenchymal markers, but increased
E-cadherin, an epithelial marker. In conclusion, these results suggest that
honokiol inhibits
metastasis by targeting the interaction between U87MG and BMECs, regulating the adhesion of U87MG to BMECs by inhibiting
VCAM-1, and regulating the invasion of U87MG through BMECs by reducing membrane permeability and EMT processes of U87MG cells.