Background Osteosarcoma (OS) is a primary bone tumor associated with locally aggressive growth and early metastatic potential that typically occurs in children and adolescents. Chinese traditional medicine Cinnamomum cassia Presl has been shown to have significant tumor-killing effect, in which cinnamaldehyde (CA) is the main active ingredient. Purpose To explore the anticancer effect of CA on the osteosarcoma cells and the possible molecular mechanism. Methods Crystal violet assay, MTT assay and colony-forming assay were used to confirm the inhibitory role of CA in the proliferation of 143B and MG63 osteosarcoma cells. Hoechst 33258 staining and flow cytometry were used to observe apoptosis. The migration and invasion role of OS cells were evaluated using transwell assays and wound healing assays. Western blotting was used to analyse the protein expression levels. Nude mice were inoculated with 143B cells to establish an orthotopic OS tumor animal model and to investigate the effects of CA on OS tumors. Results According to crystal violet assay, MTT assay and colony-forming assay, CA significantly inhibited cell proliferation. Hoechst 33258 staining and flow cytometry analysis showed that CA-induced apoptosis in a concentration-dependent manner. In addition, transwell assays and wound healing assays showed that CA inhibited the migration and invasion of osteosarcoma cells. In vivo mouse models, CA inhibited the growth of osteosarcoma. The potential mechanisms could be that CA inhibited the transcriptional activity of Wnt/β-catenin and PI3K/Akt of the osteosarcoma. Conclusion CA may inhibit the proliferation, migration, invasion and promote apoptosis of OS cells by inhibiting Wnt/β-catenin and PI3K/Akt signaling pathways. CA may be a potentially effective anti-tumor drug.

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Background: Osteosarcoma is the most common primary malignant bone neoplasm and is associated with abysmal prognosis. There are limitations of current treatment methods. Therefore, developing new agents to treat osteosarcoma is exceptionally urgent. Aim: This study aimed to evaluate the anticancer effects of evodiamine (EVO) on osteosarcoma cells and, meanwhile, to investigate the underlying mechanisms involved. Materials and Methods: The effect of EVO on the proliferation of osteosarcoma was detected by MTT assay, crystal violet assay and colony formation assay. The effects of EVO on the migration and invasion of osteosarcoma were detected by wound-healing assay and transwell assay. The effect of EVO on apoptosis of osteosarcoma was measured by Hoechst 33258 staining and cell cycle assay. The protein expression levels were detected by Western blotting assay. The activity of Wnt/β-Catenin signaling pathway was detected by luciferase reporter assay and Western blotting assay. Results: According to MTT, crystal violet and colony formation assay results, EVO significantly inhibited the cell proliferation in a dose-dependent manner. Hoechst 33258 staining assay revealed that EVO induced cell apoptosis in a concentration-dependent manner. Moreover, EVO inhibited the migration and invasion of the osteosarcoma cells. Mechanistic studies revealed that EVO suppresses metastatic through suppressing epithelial-mesenchymal transition (EMT) as indicated by elevating the expression of epithelial marker E-cadherin and reducing the expression of mesenchymal markers N-cadherin and vimentin, as well as EMT transcription factors Snail and MMPs. Subsequently, EVO induced cell cycle arrest at the G2/ M phase that correlated with reduced levels of cyclin D1 protein, while the apoptotic effects of EVO were associated with the upregulation of Bax and Bad and a decrease in Bcl-2 protein levels. Furthermore, EVO exerted the anticancer effects by suppressing Wnt/β-catenin signal pathway in osteosarcoma cells. Conclusion: In summary, EVO exhibited potent anticancer effects against human osteosarcoma cells and promoted apoptosis through suppressing Wnt/β-catenin signaling pathway. These results indicated that EVO may be regarded as a new approach for osteosarcoma treatment.

Although osteosarcoma (OS) is the most common malignant tumor among juvenile bone tumors, its treatment plan and clinical outcome have not improved significantly in recent decades. Tetrandrine (TET), a Chinese medicine that is usually used in the therapy of silicosis, hypertension and arthritis, has been confirmed by many studies to possess potent antitumour growth properties, but there are different limitations when describing specific mechanisms. Here, we found that TET can obviously prevent the proliferation, migration and invasion of both 143B and MG63 cells and promote their apoptosis in vitro. Our results for luciferase reporter and Western blotting assays show that TET may exert its antitumour activity by regulating multiplex signaling pathways, including the MAPK/Erk, PTEN/Akt, Juk and Wnt signaling pathways. Furthermore, the regulatory effect of TET on OS cells and related signaling pathways was verified again in vivo. Our findings suggest that the anticancer function of TET on human OS may be mediated by its targeting of multiple signaling pathways and that TET may be used as a single drug or in combination with other drugs during the treatment of OS.