Dimethyl fumarate suppresses metastasis and growth of melanoma cells by inhibiting the nuclear translocation of NF-κB
| Autor: | Shozo Nishida, Takao Satou, Tatsuki Itoh, Ryota Asano, Tomoya Takeda, Motohiro Imano, Masanobu Tsubaki |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Skin Neoplasms Cell Survival Dimethyl Fumarate Melanoma Experimental Apoptosis Dermatology Matrix metalloproteinase Biochemistry Metastasis Mice 030207 dermatology & venereal diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Receptors Very Late Antigen In vivo Cell Line Tumor Survivin medicine Animals Humans Viability assay Molecular Biology Cell Proliferation Cell Nucleus Dimethyl fumarate Chemistry Melanoma NF-kappa B medicine.disease Matrix Metalloproteinases Gene Expression Regulation Neoplastic 030104 developmental biology Cancer cell Cancer research Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Journal of Dermatological Science. 99:168-176 |
| ISSN: | 0923-1811 |
| Popis: | Background Malignant melanoma is among the deadliest forms of skin cancers, and its incidence has been increasing over the past decades. In malignant melanoma, activation of the nuclear factor kappa B (NF-κB) promotes survival, migration, and invasion of cancer cells. Anti-NF-κB agents for treating metastatic melanoma would be beneficial, but no such drug is approved as either monotherapy or adjuvant therapy. Dimethyl fumarate (DMF) is an approved anti-inflammatory drug already in clinical use for psoriasis and multiple sclerosis. Objective We investigated the anti-tumour effect of DMF treatment in metastatic melanoma in vitro and in vivo. Methods The cell viability was assessed via trypan blue exclusion assay. The migration and invasion was analyzed in a Boyden chamber assay. The anti-metastatic effects and anti-tumour activity of DMF was determined in an in-vivo model. The expressions of NF-κB pathway and NF-κB regulatory proteins were detected via western blotting. Results DMF decreased the cell viability, migration and invasion in vitro. In addition, DMF inhibited spontaneous metastasis and tumour growth. Mechanistically, DMF prevented the nuclear translocation of NF-κB, whereas no changes were observed in the phosphorylation levels of inhibitor of kappa B (IκB). In addition, DMF inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, DMF treatment decreased the expression of Survivin and Bcl-extra large (Bcl-XL) proteins. Conclusion Our results suggest that DMF as a novel inhibitor of NF-κB may be a potential therapeutic agent for metastatic melanoma. |
| Databáze: | OpenAIRE |
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