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Selenium metabolite methylselenol inhibits migration and invasion potential of HT1080 tumor cells
Author(s) -
Zeng Huawei,
BriskeAnderson Mary,
Idso Joseph P.,
Hunt Curtiss D.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1011-d
Subject(s) - ht1080 , matrix metalloproteinase , metabolite , chemistry , in vivo , cell migration , selenium , tissue inhibitor of metalloproteinase , carcinogen , cell cycle , metastasis , cancer research , cell , biochemistry , microbiology and biotechnology , biology , cancer , genetics , organic chemistry
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.