Paeonol Suppresses Chondrosarcoma Metastasis through Up-Regulation of miR-141 by Modulating PKCδ and c-Src Signaling Pathway

• Main Authors: Chi-Ting Horng, Po-Chuen Shieh, Tzu-Wei Tan, Wei-Hung Yang, Chih-Hsin Tang
• Format: Article
• Language: English
• Published: MDPI AG 2014-07-01
• Series: International Journal of Molecular Sciences
• Subjects: paeonol; chondrosarcoma; miR-141; metastasis
• Online Access: http://www.mdpi.com/1422-0067/15/7/11760

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.