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United States Department of Agriculture

Agricultural Research Service

Title: The Selenium Metabolite Methylselenol Inhibits the Migration and Invasion Potential of Ht1080 Tumor Cells

Authors
item ZENG, HUAWEI
item BRISKE ANDERSON, MARY
item IDSO, JOSEPH
item Hunt, Curtiss

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 8, 2006
Publication Date: June 1, 2006
Repository URL: http://handle.nal.usda.gov/10113/2091
Citation: Zeng, H., Briske-Anderson, M.J., Idso, J.P., Hunt, C. 2006. The selenium metabolite methylselenol inhibits the migration and invasion potential of HT1080 tumor cells. Journal of Nutrition. 136:1528-1532.

Interpretive Summary: Some epidemiological studies have found that Selenium (Se) status can be inversely associated with cancer risk, and intervention studies have found that supplements/high Se intakes are effective in reducing mammary, prostate, lung, colon, and liver cancer risk. In this context of cancer chemoprevention, methylselenol has been well documented as a critical component of the in vivo active Se metabolite pool. However, the underlying mechanisms remain to be elucidated. In the present study, the effects of methylselenol treatment on the growth, migration, and invasion characteristics of HT1080 cells, a well defined human invasive cancer cell line, were examined. The data provide a mechanistic basis for considering specific relationship between selenium and cancer risk. These findings will be useful information for scientists and health-care people who are working on nutrition and cancer prevention.

Technical Abstract: The anti-carcinogenic effects of selenium in nutrition are well established. Methylselenol has been hypothesized as a critical selenium metabolite for anticancer activity in vivo. To determine whether tumor cell migration, invasion, and the cell cycle characteristics are inhibited by methylselenol, we exposed HT1080 cells to methylselenol. Methylselenol, generated with seleno-L-methionine, is 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) enzymatic 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 anti-metastasic tissue inhibitor metalloproteinase 1 (TIMP 1) and metalloproteinase-2 (TIMP 2). Collectively, these results demonstrate that submicromolar concentrations of methylselenol increase both pro-metastasis MMP 2 and 9 and anti metastasis TIMP 1, 2 expression. The apparent net effect of these changes is the inhibition of carcinogenic potential/activity.

Last Modified: 9/10/2014
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