title: 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.
authors.affiliation: Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Oral & Maxillofacial Regeneration, Graduate School, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Tran Hong
authors.initials: TH
authors.lastname: Quang
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, 361-763, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, Seoul, 130-701, Republic of Korea. eckim@khu.ac.kr.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D035782:Dalbergia / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C000625809:4-parvifuran; D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: 4-Parvifuran; Apoptosis; Dalbergia odorifera; MAPK, JAK2/STAT3; Osteosarcoma