Dimethyl fumarate (DMF) functions as an orally active, brain-penetrant activator of Nrf2, leading to the upregulation of antioxidant gene expression. It triggers necroptosis in colon cancer cells via a mechanism involving GSH depletion, ROS increase, and MAPKs activation, and also induces cell autophagy, making it relevant for multiple sclerosis research[1].[2].
体内研究
In a study involving C57BL/6 mice, oral administration of dimethyl fumarate (50 mg/kg; daily; for 7 days) led to an increase in the mRNA and protein levels of Nrf2 and Nrf2-regulated cytoprotective genes. This treatment also mitigated oxidative stress and inflammation in the striatum induced by 6-OHDA[4].
体外研究
Treatment with dimethyl fumarate (20-200 μM; 24 hours) dose-dependently diminishes the viability of various cancer cells, including SGC-7901, HT29, HCT116, and CT26[1].
Specifically, at 100 μM for 3-24 hours, dimethyl fumarate significantly activates JNK, p38, and ERK in CT26 cells[1].
Dimethyl fumarate triggers necroptosis in colon cancer cells through a process involving glutathione (GSH) depletion, a rise in reactive oxygen species (ROS), and the activation of MAPK-mediated signaling pathways[1].
Dimethyl fumarate also hampers the maturation of dendritic cells (DCs) by diminishing the production of inflammatory cytokines like IL-12 and IL-6, as well as reducing the expression of MHC class II, CD80, and CD86. This effect is partly achieved through the impairment of NF-κB signaling, characterized by decreased p65 nuclear translocation and phosphorylation. Moreover, dimethyl fumarate disrupts DC maturation and the subsequent differentiation of Th1 and Th17 cells by inhibiting both NF-κB and ERK1/2-MSK1 signaling pathways[2].
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