Dimethylfumarate inhibits tumor cell invasion and metastasis by suppressing the expression and activities of matrix metalloproteinases in melanoma cells.
NF-kappaB acts as a signal transducer during tumor progression, cell invasion, and metastasis. Dimethylfumarate (DMF) is reported to inhibit tumor necrosis factor-alpha-induced nuclear entry of NF-kappaB/p65. However, only a few reports suggest that DMF inhibits tumor metastasis; also the molecular mechanisms underlying the inhibition of metastasis are poorly understood. We investigated the inhibition of tumor invasion and metastasis by DMF in a melanoma cell line, B16BL6. DMF inhibited B16BL6 cell invasion and metastasis by suppressing the expression and activities of MMPs. DMF also inhibited the nuclear entry of NF-kappaB/p65, thus inhibiting B16BL6 cell invasion and metastasis. These results suggest that DMF is potentially useful as an anti-metastatic agent for the treatment of malignant melanoma.
Yamazoe
Yuzuru
Y
Division of Pharmacotherapy, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
Tsubaki
Masanobu
M
Matsuoka
Hiroshi
H
Satou
Takao
T
Itoh
Tatsuki
T
Kusunoki
Takashi
T
Kidera
Yasuhiro
Y
Tanimori
Yoshihiro
Y
Shoji
Kaori
K
Nakamura
Haruyuki
H
Ogaki
Mitsuhiko
M
Nishiura
Saori
S
Nishida
Shozo
S
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D000069462:Dimethyl Fumarate; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005650:Fumarates / Q000627:therapeutic use* / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
D005650:Fumarates; D007166:Immunosuppressive Agents; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D051996:Transcription Factor RelA; D048049:Extracellular Signal-Regulated MAP Kinases; D000069462:Dimethyl Fumarate