ReferenceID 1136
Dihydromyricetin suppresses cell metastasis in human osteosarcoma through SP-1- and NF-κB-modulated urokinase plasminogen activator inhibition
Phytomedicine
BACKGROUND: Metastasis caused a decline in the 5-years survival rate of osteosarcoma. Therefore, developing new targeted therapeutics for osteosarcoma treatment is imperative. Dihydromyricetin (DHM) has several physiolog
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Record Fields
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- Reference Id
- 1136
- Evidence Id
- 17726
- Core Evidence Id
- 17726
- Source Reference Id
- 2256
- Herb2 Reference Id
- HBREF003053
- Subject Paper Key
- HBIN015902_34265701
- Pubmed Id
- 34265701
- Doi
- 10.1016/j.phymed.2021.153642
- Paper Title
- Dihydromyricetin suppresses cell metastasis in human osteosarcoma through SP-1- and NF-κB-modulated urokinase plasminogen activator inhibition
- Paper Abstract
- BACKGROUND: Metastasis caused a decline in the 5-years survival rate of osteosarcoma. Therefore, developing new targeted therapeutics for osteosarcoma treatment is imperative. Dihydromyricetin (DHM) has several physiological functions: it counteracts inflammation, oxidation, and antitumor properties. However, the effects of DHM on osteosarcoma and its underlying mechanisms are still not well understood. PURPOSE: In this study, we investigated the antimetastatic properties of DHM in human osteosarcoma U-2 OS and HOS cells. METHODS: The effects of DHM (0, 25, 50, 75, and 100 muM) on cell viability, migration, and invasion were examined. Western blotting, RT-PCR, and quantitative real-time PCR (QPCR) were determined urokinase plasminogen activator (uPA) expression. The expression of transcriptional factor SP-1 and NF-kappaB was determined by using immunofluorescence assay, chromatin immunoprecipitation assay, and site-directed mutagenesis luciferase reporter. RESULTS: We observed that DHM suppresses cell migration and invasion in osteosarcoma cell lines. In addition, DHM inhibits metastasis by downregulating urokinase plasminogen activator (uPA) expression. Moreover, real-time polymerase chain reaction and promoter activity assays revealed that DHM decreased uPA expression at transcription levels. Furthermore, the inhibition of uPA expression was associated with the suppression of SP-1 and NF-kappaB, which bind to the uPA promoter. Regardless of blocking or inducing the extracellular signal-regulated kinase (ERK) pathway, we verified that the DHM-related suppression of uPA and cell metastasis occurred through the p-ERK pathway. CONCLUSION: We are the first study to propose that DHM suppresses osteosarcoma metastasis through the ERK pathway and through the suppression of SP-1 and NF-kappaB to inhibit downstream uPA expression. DHM is a potential therapeutic agent for antimetastatic therapy against osteosarcoma.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- human; human osteosarcoma u-2 os and hos cells; osteosarcoma cell lines
- Experiment Type
- Cell Experiment
- Phenotype Related
- Osteosarcoma
- Paper Title Cn
- Paper Title En
- Dihydromyricetin suppresses cell metastasis in human osteosarcoma through SP-1- and NF-κB-modulated urokinase plasminogen activator inhibition
- Bilingual Status
- semi_complete