title: Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells.
abstract: Baicalein is a bioactive flavonoid that is widely used in ancient China. However, its effects on the most common primary malignant bone tumor, osteosarcoma, remain unknown. In the present study, we investigated the effects of baicalein in osteosarcoma cells. Our results indicate baicalein might be an efficacious anti-osteosarcoma drug. We found that baicalein could inhibit cell proliferation in a time- and dose-dependent manner. Additionally, we demonstrated that baicalein promotes osteosarcoma cell apoptosis, and our mechanistic studies suggest that this is mediated by caspase activation, especially caspase-3. We also showed that the down-regulation of Bcl-2 and concurrent increase in Bax and Bim levels contribute to the apoptosis induced by baicalein. In addition, we observed that baicalein induces G1 cell cycle arrest by decreasing cyclin D1 and cyclin-dependent kinase 4 (CDK4). Furthermore, our data verifies that baicalein can reduce osteosarcoma cell adhesion, migration and invasion in vitro, which indicates its potential to inhibit osteosarcoma metastasis. The decrease in expression of matrix metalloproteinases (MMP)-2 and MMP-9 may contribute to the effects of baicalein. Taken together, our results provide evidence that baicalein plays important roles in anti-osteosarcoma therapy, and thus may serve as a novel and efficient candidate agent for osteosarcoma treatment.
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Song
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Renxiong
authors.initials: R
authors.lastname: Wei
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D001859:Bone Neoplasms / Q000188:drug therapy; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D044950:Flavanones / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D044950:Flavanones; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; C006680:baicalein; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C505407:CASP3 protein, human; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9