Fisetin Suppresses Human Osteosarcoma U-2 OS Cell Migration and Invasion via Affecting FAK, uPA and NF-ĸB Signaling Pathway In Vitro

Evidence has indicated that fisetin induces cytotoxic effects in human cancer cell lines, including the inhibition of cell migration and invasion, however, the exact molecular mechanism of action of fisetin in human osteosarcoma cells remains unclear. The anti-metastatic mechanisms of fisetin in hum...

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Bibliographic Details
Published in:In vivo (Athens) 2019-05, Vol.33 (3), p.801-810
Main Authors: Chen, Jr-Kai, Peng, Shu-Fen, Lai, Kuang Chi, Liu, Hsin-Chung, Huang, Yi-Ping, Lin, Chin-Chung, Huang, An-Cheng, Chueh, Fu-Shin, Chung, Jing-Gung
Format: Article
Language:English
Subjects:
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Cell Line, Tumor
Cell Movement - drug effects
Cell Survival - drug effects
Flavonoids - pharmacology
Flavonols
Focal Adhesion Kinase 1 - metabolism
Humans
Models, Biological
NF-kappa B - metabolism
Osteosarcoma - genetics
Osteosarcoma - metabolism
Signal Transduction
Urokinase-Type Plasminogen Activator - metabolism
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Summary:Evidence has indicated that fisetin induces cytotoxic effects in human cancer cell lines, including the inhibition of cell migration and invasion, however, the exact molecular mechanism of action of fisetin in human osteosarcoma cells remains unclear. The anti-metastatic mechanisms of fisetin in human osteosarcoma U-2 OS cells were investigated in vitro. Fisetin reduced the viability of cells at different concentrations (2.5, 5 and 10 μM) as measured by flow cytometric assay. Fisetin suppressed cell mobility, migration and invasion of U-2 OS cells, as shown by wound healing assay and transwell filter chambers, respectively. The gelatin zymography assay showed that fisetin inhibited MMP-2 activity in U-2 OS cells. Results from western blotting indicated that fisetin reduced the levels of pEGFR, SOS-1, GRB2, Ras, PKC, p-ERK1/2, p-JNK, p-p-38, VEGF, FAK, RhoA, PI3K, p-AKT, NF-ĸB, uPA, MMP-7, MMP-9, and MMP-13, but increased GSK3β and E-cadherin in U-2 OS cells after 48 h of treatment. Fisetin can be used in the future, as a target for the treatment of metastasis of human osteosarcoma cells.
ISSN:0258-851X
1791-7549
DOI:10.21873/invivo.11542