Rosmarinic acid exerts an anticancer effect on osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway.

摘要: Abstract Background Osteosarcoma is the most common type of primary malignant bone tumor. This disease has exhibited a progressively lower survival rate over past several decades, which resulted in it becoming main cause death humans. Rosmarinic acid (RA), water-soluble polyphenolic phytochemical, exerts powerful anticancer effects against multiple types cancer; however, its potential on osteosarcoma remain unknown. Hence, present study investigated efficacy RA and aimed to clarify mechanisms underlying this process. Methods The cell viability, apoptosis, cycle distribution, migration, invasion, signaling molecules were analyzed by CCK-8 assay, flowcytometric analysis, wound healing Transwell proteomic use shRNAs. Results exerted anti-proliferation pro-apoptotic U2OS MG63 cells. Apoptosis was induced via extrinsic intrinsic pathways increasing Bax/Bcl-2 ratio, triggering intracellular production reactive oxygen species (ROS), reducing mitochondrial membrane (MMP), upregulating cleavage rates caspase-8, caspase-9, caspase-3. Additionally, suppressed migration invasion cells inhibiting expression levels matrix metalloproteinase-2 -9 (MMP-2 -9), are associated with weakening epithelial-mesenchymal transition (EMT). Moreover, analyses identified DJ-1 as target for RA. Several studies have indicated an oncogenic role using knockdowns lentiviral-mediated transfection shRNA, caused conspicuous suppression proliferation, well arrest progression. At molecular level, DJ-1, p-PI3K, p-Akt reduced, whereas protein phosphatase tensin homologue (PTEN) increased. Conclusion In conjunction high tissues lines, results suggested that regulation PTEN-PI3K-Akt pathway. Therefore, might be biological