title: Baicalein suppresses the viability of MG-63 osteosarcoma cells through inhibiting c-MYC expression via Wnt signaling pathway.
abstract: The major reason responsible for the poor prognosis of osteosarcoma is the malignant proliferation of osteosarcoma cells. The activated Wnt/β-catenin signaling induces c-MYC gene transcription and results in osteocytes' carcinomatous change, which contributes to osteosarcoma development, so c-MYC gene is one of the therapeutic targets. The role of multiple botanical extracts in the expression of β-catenin's target gene c-MYC in osteosarcoma MG-63 cells was tested by cellomics high content screening. Baicalein was identified as the most effective one which can inhibit the proliferation and promote the apoptosis of MG-63 cells in a dose-dependent manner by cell counting kit-8 test and fluorescence-activated cell sorting, respectively. This process was associated with the decreased levels of β-catenin and its target gene c-MYC, identified by q-PCR and Western blotting, respectively. When MG-63 cells were treated with both baicalein and JNK inhibitor SP600125, the apoptosis and expression of c-MYC were not significantly decreased. After the construct pcDNA3.1-BANCR (BRAF-regulated lncRNA 1) was transfected into MG-63 cells, RT-PCR, Western blotting and CCK-8 assay showed that BANCR was positively correlated with baicalein. These results indicated that baicalein inhibited osteosarcoma cell proliferation and promoted apoptosis by targeting c-MYC gene through Wnt signaling, in which JNK and BANCR were also involved as well as β-catenin, suggesting a new potential mechanism for us to better understand the inhibiting effect of baicalein on osteosarcoma.
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 200233, China.
authors.forename: Nengbin
authors.initials: N
authors.lastname: He
authors.forename: Zhichang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D044950:Flavanones; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; C006680:baicalein