Arctigenin Suppresses the Proliferation and Metastasis, and Induces Apoptosis and Cycle Arrest of Osteosarcoma Cells by inhibiting HMOX1 Expression

Abstract

Background: Osteosarcoma is the most common malignant bone tumor, with highly proliferative and metastatic properties. Previous studies have reported that arctigenin (Arc), a bioactive lignin compound, showed excellent anti-tumor activities in a variety of human cancers. However, its role in osteosarcoma has not been studied. Objective: We aimed to investigate the anti-tumor effects of Arc on osteosarcoma cell proliferation, migration, invasion, apoptosis, and cell cycle. Methods: Effects of Arc on osteosarcoma cell proliferation were detected by MTT and colony formation assay. Flow cytometry analysis was performed to assess the cell apoptosis and cycle arrest. Transwell assay was used to evaluate the capability of migration and invasion. qRT-PCR and Western blot were employed to determine the changes in mRNA and protein levels. Results: Arc could significantly suppress the proliferation, colony formation, and induce cell apoptosis and S phase cycle arrest of MG63 and U-2 OS cells in a dose-dependent manner. In addition, we also observed an inhibitory effect of Arc treatment on osteosarcoma cell invasion, migration, and epithelial-mesenchymal transition (EMT). HMOX1, encoding enzyme heme oxygenase-1, was predicted to be a candidate target of Arc using STITCH. Arc treatment significantly reduced the mRNA and protein levels of HMOX1. Furthermore, overexpression of HMOX1 could partly reverse the inhibitory effects of Arc on osteosarcoma cell malignant phenotypes. Conclusion: Our results suggest that Arc inhibits the proliferation, metastasis and promotes cell apoptosis and cycle arrest of osteosarcoma cells by downregulating HMOX1 expression.