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Arbutin suppresses osteosarcoma progression via miR‐338‐3p /MTHFD1L and inactivation of the AKT/mTOR pathway
- Source :
- FEBS Open Bio
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Arbutin, a natural polyphenol, inhibits OS cell viability, invasion and migration by down‐regulating MTHFD1L expression. miR‐338‐3p directly targets MTHFD1L. This regulatory action is associated with the inactivation of the AKT/mTOR signaling pathway.<br />Arbutin, a glycoside extracted from the plant Arctostaphylos uva‐ursi, has been previously reported to possess antioxidant, anti‐inflammatory and anticancer effects. Here, we investigated whether arbutin affects the proliferation of the cells of the osteosarcoma (OS) cell lines MG‐63 and SW1353. Arbutin suppressed OS cell viability in a dose‐ and time‐dependent manner, as shown by Cell Counting Kit‐8 assay. Furthermore, arbutin exposure decreased the protein levels of MTHFD1L, CCND1 and phosphorylated‐protein kinase B (AKT)/phosphorylated‐mammalian target of rapamycin (mTOR). Potential upstream miRNAs of MTHFD1L were predicted using TargetScan, PICTAR5, miRanda and miRWalk. We performed luciferase activity assays to show that miR‐338‐3p directly targets and negatively regulates the expression of MTHFD1L. Knockdown of miR‐338‐3p promoted cell invasion, migration and proliferation in arbutin‐treated OS cells via MTHFD1L. In summary, our data suggest that arbutin inhibits OS cell proliferation, migration and invasion via miR‐338‐3p/MTHFD1L and by inactivating the AKT/mTOR pathway.
- Subjects :
- 0301 basic medicine
Cell Survival
proliferation
AKT/mTOR
Bone Neoplasms
General Biochemistry, Genetics and Molecular Biology
Formate-Tetrahydrofolate Ligase
MTHFD1L
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cyclin D1
Aminohydrolases
Cell Movement
Multienzyme Complexes
Cell Line, Tumor
Humans
Viability assay
Protein kinase B
Research Articles
miR‐338‐3p
PI3K/AKT/mTOR pathway
Methylenetetrahydrofolate Dehydrogenase (NADP)
Osteosarcoma
Kinase
Cell growth
TOR Serine-Threonine Kinases
Arbutin
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
chemistry
Cell culture
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Cancer research
Proto-Oncogene Proteins c-akt
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 22115463
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- FEBS Open Bio
- Accession number :
- edsair.doi.dedup.....42852d655141216a3f71fe382ff472f4