Honokiol exerts an anticancer effect in T98G human glioblastoma cells through the induction of apoptosis and the regulation of adhesion molecules

Abstract

Glioblastoma is one of the most lethal and common malignant human brain tumors, with aggressive proliferation and highly invasive properties. Honokiol derived from Magnolia officinalis is able to cross the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), suggesting a strong possibility that it could be an effective drug for the treatment of brain tumors, including glioblastoma. Thus, we investigated the effects of honokiol on the expression of adhesion molecules in TNF-α-stimulated endothelial cells, and cancer growth and invasion were determined in T98G human glioblastoma cells. Honokiol dose-dependently inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with TNF-α for 6 h. Pretreatment with honokiol significantly reduced the adhesion of T98G cells to HUVECs. Moreover, honokiol inhibited the invasion of T98G cells, suggesting that honokiol has an anti-metastatic effect. In addition, honokiol increased the cytotoxicity of T98G cells in a dose- and time-dependent manner as assayed by MTT. TUNEL assay showed that honokiol significantly induced apoptosis in T98G cells at doses of 10 µM or more. The induction of apoptotic cell death was mediated by the downregulation of the anti-apoptotic protein Bcl-2 and the upregulation of the pro-apoptotic protein Bax. Taken together, the results of this study suggest that honokiol exerts an anticancer effect by preventing metastasis and inducing apoptotic cell death of brain tumor cells.

Honokiol inhibits U87MG human glioblastoma cell invasion through endothelial cells by regulating membrane permeability and the epithelial-mesenchymal transition

“…In this study, we aimed to investigate the effect of honokiol on the cell invasion process of U87MG human glioblastoma cells through brain microvascular endothelial cells (BMECs) and its possible mechanisms. Thus, first, we examined the cell viability of U87MG cells and BMECs in response to honokiol in a lower range compared to the previous study (22). When U87MG cells and BMECs were treated with indicated honokiol (1-20 µM) for 24 h, the results revealed that honokiol significantly decreased the cell viability of U87MG only at doses of 20 µM (Fig.…”

“…Honokiol is reported to cross the BBB and the BCSFB and to overcome immunoresistance in glioma, strongly suggesting that it could be an effective drug for the treatment of brain tumors, including glioblastoma. Our previous study demonstrated that honokiol induced apoptotic cell death and inhibited cell invasion through regulation of ICAM-1 and VCAM-1 in human glioblastoma T98G cells (22). Recently, it was reported that tumors, including gliomas, contain a small subpopulation of cancer stem cells (CSCs).…”

“…Notably, treatment with honokiol may be a potential strategy to overcome immunoresistance in glioma (20), as honokiol can cross the BBB and the BCSFB (21). In addition, our previous study demonstrated that honokiol induces apoptotic cell death through the upregulation of the Bax/Bcl-2 ratio and inhibits invasion through the regulation of ICAM-1 and VCAM-1 in human glioblastoma T98G cells (22). Based on these results, honokiol may represent an effective drug for the treatment of brain tumors, specifically glioblastoma.…”

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

“…Many studies have showed that lignans containing typical aromatic rings can cross the BBB [46]. For example, the typical lignan honokiol is able to cross the BBB and the blood-cerebrospinal fluid barrier, and it exerts an anticancer effect [47,48]. Furthermore, six lignans have been detected directly in rat brain tissue after oral administration of lignan extracts [49].…”

Honokiol inhibits bladder cancer cell invasion through repressing SRC-3 expression and epithelial-mesenchymal transition

“…As one of the major lignans with high bioavailability, honokiol exhibits multiple biological properties, including muscle relaxant, neuroprotective, anti-inflammatory and anticancer effects (14)(15)(16)(17)(18)(19). However, whether honokiol exhibits an effect UBC cell migration and invasion remains unclear.…”