Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 405, Issue 1-2, Pages 187-196Publisher
SPRINGER
DOI: 10.1007/s11010-015-2410-6
Keywords
Osteosarcoma; Baicalein; c-MYC; beta-catenin; Wnt; BANCR
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The major reason responsible for the poor prognosis of osteosarcoma is the malignant proliferation of osteosarcoma cells. The activated Wnt/beta-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 beta-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 beta-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 beta-catenin, suggesting a new potential mechanism for us to better understand the inhibiting effect of baicalein on osteosarcoma.
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