4-parvifuran inhibits metastatic and invasive actions through the JAK2/STAT3 pathway in osteosarcoma cells.

Abstract

This study was performed to examine the anticancer and anti-metastatic effects of 4-parvifuran (PVN), a novel flavonoid isolated from the heartwood of Dalbergia odorifera, and to study its underlying signaling pathway in human osteosarcoma cells. In the present study, PVN was found to inhibit cell proliferation in a concentration- and time-dependent manner in the human osteosarcoma cell lines studied (MG-63 and U-2 OS) and induce apoptosis, as evidenced by Annexin V+ and TUNEL+ cells. Cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 were up-regulated while anti-apoptotic proteins including Bcl-2, Bcl-xL, and survivin were down-regulated after treatment with PVN. Matrigel cell migration assay, invasion assay, and soft agar assay were used to show that PVN effectively suppressed cell migration and invasion and colony formation in osteosarcoma cells. Protein and mRNA levels of MMP-2 and MMP-9 were reduced by PVN in a concentration-dependent manner. Furthermore, PVN inhibited Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), mitogen-activated protein kinases (MAPKs) including JNK, ERK, p38 kinase, and cAMP response element-binding protein (CREB). Therefore, this is the first study to demonstrate that PVN might be a novel anticancer and anti-metastatic agent for the treatment of osteosarcoma through the inhibition of JAK2/STAT3, MAPKs, and CREB signaling pathways.