Silibinin inhibits invasive properties of human glioblastoma U87MG cells through suppression of cathepsin B and nuclear factor kappa B-mediated induction of matrix metalloproteinase 9.
Glioblastoma multiforme remains one of the most devastating human malignancies because of its high infiltrative capacity. This study aimed to investigate the effects of silibinin on human glioblastoma U87MG cells. The microculture tetrazolium test, bromodeoxyuridine cell proliferation assay, cell-based nuclear factor kappa B (NF-[kappa]B) activation assessment, cathepsin B activity assay, gelatin zymography, and quantitative real-time reverse transcription-PCR were performed to appraise the effects of silibinin on the metabolic activity, DNA synthesis, NF-[kappa]B phosphorylation, cathepsin B activity, and gelatinolytic activity of U87 cells. Silibinin inhibited metabolic activity, cell proliferation, NF-[kappa]B activation, cathepsin B enzymatic levels, and gelatinase B activity in U87 cells. In addition, an expressive decrease in mRNA levels of matrix metalloproteinase-9, cathepsin B, urokinase plasminogen activator receptor, urokinase plasminogen activator, and intercellular adhesion molecule 1 coupled with a significant induction in transcriptional levels of stefin A was observed. Altogether, these issues show for the first time that silibinin treatment could trammel invasive features of a highly invasive human glioma cell line, U87, through suppression of NF-[kappa]B-mediated stimulation of matrix metalloproteinase-9. Furthermore, silibinin might cripple the activation of gelatinase B by cramping transcriptional and enzymatic activities of cathepsin B in U87 cells.
Momeny
Majid
M
Hematology, Oncology and Bone Marrow Transplantation Research Center, Tehran, Iran.
Malehmir
Mohsen
M
Zakidizaji
Majid
M
Ghasemi
Reza
R
Ghadimi
Habibeh
H
Shokrgozar
Mohammad A
MA
Emami
Amir H
AH
Nafissi
Shahriar
S
Ghavamzadeh
Ardeshir
A
Ghaffari
Seyed H
SH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055312:Cystatin A / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000819:agonists*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology
D000970:Antineoplastic Agents; D055312:Cystatin A; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D012838:Silymarin; D018799:Intercellular Adhesion Molecule-1; D000077385:Silybin; C026407:CSTA protein, human; D002401:Cathepsin B