title: Suppression of the migration and invasion is mediated by triptolide in B16F10 mouse melanoma cells through the NF-kappaB-dependent pathway.
abstract: Melanoma cancer is one of the major causes of death in humans worldwide. Triptolide is one of the active components of Tripterygium wilfordii Hook F, and has biological activities including induced cell cycle arrest and induction of apoptosis but its antimetastatic effects on murine melanoma cells have not yet been elucidated. Herein, we investigated the effect of triptolide on the inhibition of migration and invasion and possible associated signal pathways in B16F10 murine melanoma cancer cells. Wound healing assay and Matrigel Cell Migration Assay and Invasion System demonstrated that triptolide marked inhibiting the migration and invasion of B16F10 cells. Gelatin zymography assay demonstrated that triptolide significantly inhibited the activities of matrix metalloproteinases-2 (MMP-2). Western blotting showed that triptolide markedly reduced CXCR4, SOS1, GRB2, p-ERK, FAK, p-AKT, Rho A, p-JNK, NF-κB, MMP-9, and MMP-2 but increased PI3K and p-p38 and COX2 after compared to the untreated (control) cells. Real time PCR indicated that triptolide inhibited the gene expression of MMP-2, FAK, ROCK-1, and NF-κB but did not significantly affect TIMP-1 and -2 gene expression in B16F10 cells in vitro. EMSA assay also showed that triptolide inhibited NF-κB DNA binding in a dose-dependent manner. Confocal laser microscopy examination also confirmed that triptolide inhibited the expression of NF-κB in B16F10 cells. Taken together, we suggest that triptolide inhibited B16F10 cell migration and invasion via the inhibition of NF-κB expression then led to suppress MMP-2 and -9 expressions. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1974-1984, 2016.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan, ROC.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Jao
authors.affiliation: School of Dentistry, China Medical University, Taichung, 404, Taiwan, ROC.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.affiliation: School of Pharmacology, China Medical University, Taichung, 404, Taiwan, ROC.
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.affiliation: School of Pharmacology, China Medical University, Taichung, 404, Taiwan, ROC.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 404, Taiwan, ROC.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Liu
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan, ROC.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Liao
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, 500, Taiwan, ROC.
authors.forename: Bin-Chuan
authors.initials: BC
authors.lastname: Ji
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 404, Taiwan, ROC.|Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, 404, Taiwan, ROC.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan, ROC.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan, ROC.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010616:Phenanthrenes / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; C001899:triptolide
keywords: B16F10 mouse melanoma cells; NF-kappaB-dependent pathway; invasion; migration; triptolide