Long exposure of non-cytotoxic concentrations of methylselenol suppresses the invasive potential of B16F10 melanoma.
To assess the inhibitory effects of methylselenol on the invasion of murine B16F10 melanoma cells, we carried out in vivo and in vitro experiments using Se-methylselenocysteine (Se-MSC) and selenomethionine (SeMet), respectively. In an animal experiment, the supplementation of drinking water with Se-MSC (4 ppm Se) led to a significant increase in Se levels in the lung, liver and serum in mice. Mice given a mash diet or water supplemented with Se-MSC (2, 4 and 6 ppm Se in the mash diet, and 2 and 4 ppm Se in the drinking water) displayed an almost completely diminished pulmonary metastasis of B16F10 melanoma cells and an enhanced survival, compared to the control mice which were given a basal diet. Treatment with non-cytotoxic concentrations of SeMet (2.5, 5 and 10 microM plus 0.02 U/ml METase, methioninase) induced a substantial decrease in the expression of integrin alphavbeta3, the FN receptor and adhesion ability to vitronectin (VN) and fibronectin (FN) in B16F10 melanoma cells. Moreover, these compounds suppressed gelatinase activity, invasive ability and wound migration in the culture system. SeMet-METase prevented the conversion of pro-MMP-9 to its active form and decreased pro-MMP-2 activities in a zymogram. The pre-treatment of B16F10 melanoma cells with SeMet-METase led to a decrease in pulmonary metastasis and extended survival in mice injected with tumor cells. Collectively, our results indicate that integrin expression is crucial in promoting the metastatic phenotype in murine B16F10 melanoma cells by supporting specific adhesive and invasive properties, suggesting that Se-MSC effectively reduces the metastasis of B16F10 melanoma cells as a nutritional adjuvant. Methylselenol may also contribute to the suppression of integrin expression.
Kim
Aeyung
A
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Jung
Ji-Yong
JY
Son
Minsik
M
Lee
Sang-Han
SH
Lim
Jong-Seok
JS
Chung
An-Sik
AS
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D019587:Dietary Supplements; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology*; D000432:Methanol / Q000031:analogs & derivatives; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D017279:Selenocysteine / Q000031:analogs & derivatives; D018038:Sodium Selenite / Q000494:pharmacology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D005353:Fibronectins; D039302:Integrin alphaVbeta3; D016023:Integrins; D016566:Organoselenium Compounds; D019096:Vitronectin; D017279:Selenocysteine; C019003:methaneselenol; D018093:Gelatinases; D018038:Sodium Selenite; D003545:Cysteine; C002979:selenomethylselenocysteine; D000432:Methanol