ReferenceID 6151
Rosmarinic acid exerts an anticancer effect on osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway
Phytomedicine
BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor. This disease has exhibited a progressively lower survival rate over the past several decades, which has resulted in it becoming a main cau
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 6151
- Evidence Id
- 22741
- Core Evidence Id
- 22741
- Source Reference Id
- 5564
- Herb2 Reference Id
- HBREF006361
- Subject Paper Key
- HBIN042438_32088353
- Pubmed Id
- 32088353
- Doi
- 10.1016/j.phymed.2020.153186
- Paper Title
- Rosmarinic acid exerts an anticancer effect on osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway
- Paper Abstract
- BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor. This disease has exhibited a progressively lower survival rate over the past several decades, which has resulted in it becoming a main cause of death in humans. Rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts powerful anticancer effects against multiple types of cancer; however, its potential effects on osteosarcoma remain unknown. Hence, the present study investigated the efficacy of RA against osteosarcoma and aimed to clarify the mechanisms underlying this process. METHODS: The effects of RA on cell viability, apoptosis, cell cycle distribution, migration, invasion, and signaling molecules were analyzed by CCK-8 assay, flowcytometric analysis, wound healing assay, Transwell assay, proteomic analysis, and use of shRNAs. RESULTS: RA exerted anti-proliferation and pro-apoptotic effects on U2OS and MG63 osteosarcoma cells. Apoptosis was induced via extrinsic and intrinsic pathways by increasing the Bax/Bcl-2 ratio, triggering the intracellular production of reactive oxygen species (ROS), reducing the mitochondrial membrane potential (MMP), and upregulating the cleavage rates of caspase-8, caspase-9, and caspase-3. Additionally, RA suppressed the migration and invasion of osteosarcoma cells by inhibiting the expression levels of matrix metalloproteinase-2 and -9 (MMP-2 and -9), which are associated with a weakening of the epithelial-mesenchymal transition (EMT). Moreover, proteomic analyses identified DJ-1 as a potential target for RA. Several studies have indicated an oncogenic role for DJ-1 using knockdowns via the lentiviral-mediated transfection of shRNA, which caused the conspicuous suppression of cell proliferation, migration, and invasion as well as the arrest of cell cycle progression. At the molecular level, the expression levels of DJ-1, p-PI3K, and p-Akt were reduced, whereas the protein levels of phosphatase and tensin homologue (PTEN) were increased. CONCLUSION: In conjunction with the high levels of DJ-1 expression in osteosarcoma tissues and cell lines, the present results suggested that RA exhibited anticancer effects in osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway. Therefore, DJ-1 might be a biological target for RA in osteosarcoma cells.
- Journal
- Phytomedicine
- Publish Year
- 2020
- Experiment Subject
- human; cell lines; mg63 osteosarcoma cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Osteosarcoma; Cancer; Malignant Bone Tumor
- Paper Title Cn
- Paper Title En
- Rosmarinic acid exerts an anticancer effect on osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway
- Bilingual Status
- semi_complete