title: Paeonol suppresses chondrosarcoma metastasis through up-regulation of miR-141 by modulating PKCδ and c-Src signaling pathway.
abstract: Chondrosarcoma, a primary malignant bone cancer, has potential for local invasion and distant metastasis, especially to the lungs. Patients diagnosed with it show poor prognosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of traditional Chinese remedy Paeonia lactiflora Pallas, exhibits anti-inflammatory and anti-tumor activity; whether paeonol regulates metastatic chondrosarcoma is largely unknown. Here, we find paeonol do not increase apoptosis. By contrast, at non-cytotoxic concentrations, paeonol suppresses migration and invasion of chondrosarcoma cells. We also demonstrate paeonol enhancing miR-141 expression and miR-141 inhibitor reversing paeonol-inhibited cell motility; paeonol also reduces protein kinase C (PKC)d and c-Src kinase activity. Since paeonol inhibits migration and invasion of human chondrosarcoma via up-regulation of miR-141 via PKCd and c-Src pathways, it thus might be a novel anti-metastasis agent for treatment of metastatic chondrosarcoma.
authors.affiliation: Medical Education Center, Kaohsiung Armed Force General Hospital, Kaohsiung 802, Taiwan. mtc9042@yahoo.com.tw.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Horng
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung 907, Taiwan. pochuen@mail.tajen.edu.tw.
authors.forename: Po-Chuen
authors.initials: PC
authors.lastname: Shieh
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. twtan@mail.cmu.edu.tw.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Tan
authors.affiliation: Department of Orthopedic Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung 403, Taiwan. u766018@ms42.hinet.net.
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Yang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. twtan@mail.cmu.edu.tw.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002813:Chondrosarcoma / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000098:Acetophenones; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; C013638:paeonol; D019061:src-Family Kinases; D051745:Protein Kinase C-delta