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4-parvifuran inhibits metastatic and invasive actions through the JAK2/STAT3 pathway in osteosarcoma cells
Hyung-Mun Yun1, Kyung-Ran Park2, Tran Hong Quang3
1Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
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.
Insights
4-parvifuran (PVN), a novel flavonoid, demonstrates significant anticancer and anti-metastatic properties in human osteosarcoma cells. PVN inhibits proliferation, induces apoptosis, and suppresses migration by targeting key signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma is a primary bone malignancy with high metastatic potential.
- Novel therapeutic agents are needed to combat osteosarcoma progression and metastasis.
Purpose of the Study:
- To investigate the anticancer and anti-metastatic effects of 4-parvifuran (PVN) in human osteosarcoma cells.
- To elucidate the underlying signaling pathways affected by PVN treatment.
Main Methods:
- Human osteosarcoma cell lines (MG-63, U-2 OS) were treated with PVN.
- Cell proliferation, apoptosis (Annexin V, TUNEL), migration, invasion, and colony formation were assessed.
- Western blotting and qRT-PCR were used to analyze protein and mRNA expression of key signaling molecules (PARP, caspase-3, Bcl-2 family, MMP-2, MMP-9, JAK2/STAT3, MAPKs, CREB).
Main Results:
- PVN inhibited osteosarcoma cell proliferation and induced apoptosis in a dose- and time-dependent manner.
- PVN significantly suppressed cell migration, invasion, and soft agar colony formation.
- PVN treatment led to the upregulation of cleaved PARP and caspase-3, and downregulation of anti-apoptotic proteins (Bcl-2, Bcl-xL, survivin).
- PVN reduced MMP-2 and MMP-9 levels and inhibited the JAK2/STAT3, MAPKs (JNK, ERK, p38), and CREB signaling pathways.
Conclusions:
- PVN exhibits potent anticancer and anti-metastatic activities against human osteosarcoma.
- PVN exerts its effects by inhibiting critical signaling pathways including JAK2/STAT3, MAPKs, and CREB.
- PVN represents a promising novel therapeutic candidate for osteosarcoma treatment.