QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zeng, H. Articles by Hunt, C. D. Search for Related Content PubMed PubMed Citation Articles by Zeng, H. Articles by Hunt, C. D.

---

Nutrition and Disease

The Selenium Metabolite Methylselenol Inhibits the Migration and Invasion Potential of HT1080 Tumor Cells

United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034

¹ To whom correspondence should be addressed. E-mail: hzeng{at}gfhnrc.ars.usda.gov.

There is increasing evidence for the efficacy of certain forms of selenium as cancer-chemopreventive compounds. Methylselenol has been hypothesized to be a critical selenium metabolite for anticancer activity in vivo. To determine whether tumor cell migration, invasion, and cell cycle characteristics are inhibited by methylselenol, we exposed HT1080 cells to methylselenol. Methylselenol was generated with seleno-L-methionine (a substrate for methioninase). Submicromolar methylselenol exposure led to an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, indicating slower cell growth. Furthermore, methylselenol inhibited the migration and invasion rate of the tumor cells by up to 53 and 76%, respectively, when compared with the control tumor cells. Although all cells had increased matrix metalloproteinase (MMP) enzyme activities of pro-MMP-2 and pro-MMP-9, the active form of MMP-2 was decreased in HT1080 cells cultured with methylselenol. In addition, methylselenol increased the protein levels of antimetastasic tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2. Collectively, these results demonstrate that submicromolar concentrations of methylselenol increase both prometastasis MMP-2 and MMP-9 and antimetastasis TIMP-1 and TIMP-2 expression. The apparent net effect of these changes is the inhibition of pro-MMP-2 activation and carcinogenic potential or activity.

KEY WORDS: • selenium • cell cycle • migration • invasion • cancer

This article has been cited by other articles:

				H. Zeng, M. Wu, and J. H. Botnen Methylselenol, a Selenium Metabolite, Induces Cell Cycle Arrest in G1 Phase and Apoptosis via the Extracellular-Regulated Kinase 1/2 Pathway and Other Cancer Signaling Genes J. Nutr., September 1, 2009; 139(9): 1613 - 1618. [Abstract] [Full Text] [PDF]

				J.-M. Park, A. Kim, J.-H. Oh, and A.-S. Chung Methylseleninic acid inhibits PMA-stimulated pro-MMP-2 activation mediated by MT1-MMP expression and further tumor invasion through suppression of NF-{kappa}B activation Carcinogenesis, April 1, 2007; 28(4): 837 - 847. [Abstract] [Full Text] [PDF]