Dimethyl fumarate suppresses metastasis and growth of melanoma cells by inhibiting the nuclear translocation of NF-κB.

Journal of Dermatological Science
Tomoya TakedaShozo Nishida

Abstract

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. We investigated the anti-tumour effect of DMF treatment in metastatic melanoma in vitro and in vivo. 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. 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 (Iκ...Continue Reading

Citations

Oct 18, 2020·Pharmaceuticals·Stephanie KourakisEmma Rybalka
Feb 13, 2021·Antioxidants·Shiri LiHirohito Ichii
Oct 30, 2020·International Journal of Molecular Sciences·Masanobu TsubakiShozo Nishida
Mar 6, 2021·Orphanet Journal of Rare Diseases·Stephanie KourakisEmma Rybalka

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