The selenium metabolite methylselenol inhibits the migration and invasion potential of HT1080 tumor cells.
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.
Zeng
Huawei
H
United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034, USA. hzeng@gfhnrc.ars.usda.gov
Briske-Anderson
Mary
M
Idso
Joseph P
JP
Hunt
Curtiss D
CD
D002453:Cell Cycle / Q000187:drug effects*; D000432:Methanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D016566:Organoselenium Compounds; D019714:Tissue Inhibitor of Metalloproteinases; C019003:methaneselenol; D000432:Methanol