Honokiol exerts an anticancer effect in T98G human glioblastoma cells through the induction of apoptosis and the regulation of adhesion molecules.
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.
Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Jae Ju
JJ
Jeong
Jae Heun
JH
Lee
Ki Churl
KC
Chang
Hye Jung
HJ
Kim
D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D017705:Lignans / Q000008:administration & dosage*; D031566:Magnolia / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D017705:Lignans; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols