Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9.
ADAM Proteins
/ metabolism
Antineoplastic Agents
/ chemistry
Carcinoma, Renal Cell
/ drug therapy
Cathepsins
/ metabolism
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Flavonoids
/ chemistry
Flavonols
Humans
Kidney Neoplasms
/ drug therapy
MAP Kinase Signaling System
/ drug effects
Membrane Proteins
/ metabolism
Molecular Structure
Neoplasm Metastasis
/ drug therapy
Structure-Activity Relationship
Tumor Cells, Cultured
ADAM9
CTSS
fisetin
invasion
migration
proliferation
renal cell carcinoma
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
21 08 2019
21 08 2019
Historique:
received:
18
07
2019
revised:
16
08
2019
accepted:
19
08
2019
entrez:
24
8
2019
pubmed:
24
8
2019
medline:
19
5
2020
Statut:
epublish
Résumé
Fisetin, a natural flavonoid, is known to have anticarcinogenic effects against several cancers, but its role in mediating renal cell carcinoma (RCC) progression has not been delineated. Cell viability, cytotoxicity, and cell cycle distribution were measured using the 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and propidium iodide staining with flow cytometry. The in vitro migration and invasion assay was used to examine in vivo cell migration and invasion. Human protease antibody array analysis was conducted with cell migration/invasion-related proteins. Western blotting and quantitative reverse transcription polymerase chain reaction were used for assessing protein expression related to the cell cycle, cell invasion, and mitogen-activated protein kinase (MAPK) signaling pathway. We found that fisetin significantly inhibited cell viability through cell cycle arrest in the G2/M phase, in addition to downregulating cyclin D1 and upregulating p21/p27. Fisetin inhibited the migration and invasion of human RCC cells through the downregulation of CTSS and a disintegrin and metalloproteinase 9 (ADAM9). Fisetin also upregulated ERK phosphorylation in 786-O and Caki-1 cells. Furthermore, treatment with a MEK inhibitor (UO126) reduced the inhibitory effects of fisetin on the metastasis of RCC cells through the ERK/CTSS/ADAM9 pathway. Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.
Identifiants
pubmed: 31438640
pii: cells8090948
doi: 10.3390/cells8090948
pmc: PMC6770737
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Flavonoids
0
Flavonols
0
Membrane Proteins
0
Cathepsins
EC 3.4.-
cathepsin S
EC 3.4.22.27
ADAM Proteins
EC 3.4.24.-
ADAM9 protein, human
EC 3.4.24.-
fisetin
OO2ABO9578
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests
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