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

Abstract

BACKGROUND/AIM:

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.

MATERIALS AND METHODS:

The anti-metastatic mechanisms of fisetin in human osteosarcoma U-2 OS cells were investigated in vitro.

RESULTS:

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.

CONCLUSION:

Fisetin can be used in the future, as a target for the treatment of metastasis of human osteosarcoma cells.

• Authors: Jr-Kai Chen, Shu-Fen Peng, Kuang Chi Lai, Hsin-Chung Liu, Yi-Ping Huang, Chin-Chung Lin, An-Cheng Huang, Fu-Shin Chueh, Jing-Gung Chung
• Journal: In vivo (Athens, Greece) (In Vivo) 2019 May-Jun Vol. 33 Issue 3 Pg. 801-810 ISSN: 1791-7549 [Electronic] Greece
• PMID: 31028200 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Flavonoids
• Flavonols
• NF-kappa B
• Focal Adhesion Kinase 1
• PTK2 protein, human
• Urokinase-Type Plasminogen Activator
• fisetin

Topics

• Bone Neoplasms (genetics, 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, metabolism)
• Signal Transduction
• Urokinase-Type Plasminogen Activator (metabolism)