Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

• DOI: 10.1111/cas.12852
• Publication Date: 2015-11-23T17:14:43Z
• Authors: Ki Mo Kim; A‐Rang Im; Seung Hyung Kim; Jin Won Hyun; Sungwook Chae
• Keywords: COX-2; melanoma cells; metastasis; migration; timosaponin AIII; Cyclooxygenase 2 Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Melanoma, Experimental; NF-kappa B; Antineoplastic Agents; Original Articles; Saponins; Transfection; Dinoprostone; 3. Good health; Mice, Inbred C57BL; Mice; Cell Movement; Cyclooxygenase 2; Cell Line, Tumor; Animals; Humans; Receptors, Prostaglandin E; Neoplasm Invasiveness; Steroids; RNA, Small Interfering

Melanoma is the leading cause of death from skin disease, due in large part to its propensity metastasize. We examined effects timosaponin AIII, a compound isolated Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and molecular mechanisms underlying these using B16-F10 WM-115 cells lines. Overexpression COX-2, metabolite prostaglandin E2 (PGE2), PGE2 receptors (EP2 EP4) promoted vitro. Exposure AIII resulted concentration-dependent inhibition migration, which was associated with reduced levels PGE2, receptors. Transient transfection COX-2 siRNA also inhibited migration. 12-O-tetradecanoylphorbal-13-acetate enhanced whereas 12-O-tetradecanoylphorbal-13-acetate-induced basal EP2 EP4. Moreover, activation nuclear factor-kappa B (NF-κB), an upstream regulator cells. Consistent our vitro findings, vivo studies showed that treatment significantly total number metastatic nodules mouse lung improved histological alterations B16-F10-injected C57BL/6 mice. In addition, mice treated expression NF-κB lung. Together, results indicate has capacity inhibit essential step process metastasis, by inhibiting NF-κB,