Selenium inhibits migration of murine melanoma cells via down-modulation of IL-18 expression.
Melanoma is an aggressive form of skin cancer due to its rapid metastasis. Recently, several studies have reported that selenium can prevent metastasis of melanoma cells, but the mechanism of this anti-metastatic ability is not fully understood. In this study, we investigated the effect of selenium on cell migration in melanoma and on tumor metastasis in mice. Interestingly, tumor metastasis was suppressed by selenium in a mouse model. Cell migration was measured by a wound-healing assay using selenium-treated melanoma cells. Treatment with a non-cytotoxic concentration of selenium suppressed migration of melanoma cells in a dose-dependent manner. In addition, we found decreased HIF-1α and VEGF expression in selenium-treated melanoma cells as compared to non-treated control cells. Mechanistically, our studies show that selenium inhibits IL-18 gene expression in a dose-dependent manner. IL-18 protein level was suppressed by treatment with selenium. The wound-healing assay revealed that the anti-metastatic effect of selenium was abrogated by treatment with exogenous IL-18. These results suggest that selenium might be a potent inhibitor of the metastatic capacity of melanoma cells, via down-modulation of IL-18 expression.
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan, Republic of Korea.
Hyunkeun
H
Song
Jiyoung
J
Kim
Hyun-Kyung
HK
Lee
Hyun-jin
HJ
Park
Joohyung
J
Nam
Ga Bin
GB
Park
Yeong Seok
YS
Kim
DaeHo
D
Cho
Dae Young
DY
Hur
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D012643:Selenium / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014131:Trace Elements / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020382:Interleukin-18; D014131:Trace Elements; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D012643:Selenium