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

Abstract

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.

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

“…We examined the role of TGF-β/Smad signaling in the progression of fibrosis. We found that expression levels of TGF-β1, p-Smad2, and p-Smad3 induced by pressure overload were attenuated in Hyp-treated mice, which is consistent with previous findings [25]. Our data showed that Hyp reduced TGF-β/Smad signaling in hypertrophied hearts and inhibited collagen synthesis.…”

Role of osteopontin in osteosarcoma

“…Osteoblastic differentiation is essential for proper bone formation [30], and disruption in the differentiation of osteoblast from mesenchymal stem cells is considered to be the main cause of OS [31]. OPN is reported to be necessary for the differentiation of osteoblast through the avb3-integrin-mediated cell signaling [32,33]. Alteration in OPN level may disrupt the differentiation signaling pathway which failed to promote the differentiation of OS cells, enhanced OS tumor growth and exhibited possible differentiation defects in OS cells [31,34].…”

Phytochemical Evaluation of Chrozophora rottleri (Geiseler) A. Juss. ex Spreng.

“…Demethylation of the compound VII with HI gave a solid, which was found to be identical in all respect with compound VI. These observations suggested that the compound VII must be naringenin 4"-methyl ether (Zhang et al, 2014;Grayer, 1989). This was further supported by the appearance of peak at m/z, 286 (M+, 2) in EIMS, in agreement with the molecular formula C16 H14 O5 of the compoundVII.…”

“…(Jayprakasam, 1993). Based on these observations the flavanone was identified as 5, 7, 4"-trihydroxy flavanone (Buckingham, 1995) (naringenin) (Figure 6) and the identity confirmed by CO-PC with authentic sample (Zhang et al, 2014) yellow under UV/NH3. It had λmax (MeOH) 287, 325sh and Rf (Table 3) characteristic of a typical flavanone.…”