Journal Article

Hyperoside, a Flavonoid Compound, Inhibits Proliferation and Stimulates Osteogenic Differentiation of Human Osteosarcoma Cells

Ying, Mei-Dan, Zhou, Zhi-Hong, Li, Hang, Lin, Ding-Sheng, Ye, Zhao-Ming, Wu, Yong-Ping, Zhang, Ning

2014

Overview

Osteosarcoma, one of the most common malignant bone tumours, is generally considered a differentiation disease caused by genetic and epigenetic disruptions in the terminal differentiation of osteoblasts. Novel therapies based on the non-cytotoxic induction of cell differentiation-responsive pathways could represent a significant advance in treating osteosarcoma; however, effective pharmaceuticals to induce differentiation are lacking. In the present study, we investigated the effect of hyperoside, a flavonoid compound, on the osteoblastic differentiation of U2OS and MG63 osteosarcoma cells in vitro. Our results demonstrated that hyperoside inhibits the proliferation of osteosarcoma cells by inducing G0/G1 arrest in the cell cycle, without causing obvious cell death. Cell migration assay further suggested that hyperoside could inhibit the invasion potential of osteosarcoma cells. Additionally, osteopontin and runt-related transcription factor 2 protein levels and osteocalcin activation were upregulated dramatically in hyperoside-treated osteosarcoma cells, suggesting that hyperoside may stimulates osteoblastic differentiation in osteosarcoma cells. This differentiation was accompanied by the activation of transforming growth factor (TGF)-β and bone morphogenetic protein-2, suggesting that the hyperoside-induced differentiation involves the TGF-β signalling pathway. To our knowledge, this study is the first to evaluate the differentiation effect of hyperoside in osteosarcoma cells and assess the possible potential for hyperoside treatment as a future therapeutic approach for osteosarcoma differentiation therapy.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Activation / Apoptosis / Bioavailability / Biocompatibility / Biology and Life Sciences / Biomedical materials / Bone cancer / Bone morphogenetic protein 2 / Bone morphogenetic proteins / Bone Neoplasms - drug therapy / Bone Neoplasms - metabolism / Bone Neoplasms - pathology / Bone tumors / Cancer therapies / Cell cycle / Cell death / Cell differentiation / Cell Differentiation - drug effects / Cell Line, Tumor / Cell migration / Cell proliferation / Cell Proliferation - drug effects / Chemotherapy / Cytotoxicity / Differentiation (biology) / Epigenetic inheritance / Flavonoids / Flavonoids - pharmacology / Growth factors / Hospitals / Humans / Medical prognosis / Medicine / Medicine and Health Sciences / Metastasis / Osteoblastogenesis / Osteoblasts / Osteoblasts - metabolism / Osteoblasts - pathology / Osteocalcin / Osteogenesis - drug effects / Osteopontin / Osteosarcoma / Osteosarcoma - drug therapy / Osteosarcoma - metabolism / Osteosarcoma - pathology / Osteosarcoma cells / Polyphenols / Quercetin - analogs & derivatives / Quercetin - pharmacology / Sarcoma / Signal transduction / Signaling / Stem cells / Transforming growth factors / Tumors