arbutin and Osteosarcoma

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.

Topics: Aminohydrolases; Arbutin; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Survival; Formate-Tetrahydrofolate Ligase; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Methylenetetrahydrofolate Dehydrogenase (NADP); MicroRNAs; Multienzyme Complexes; Osteosarcoma; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases