Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 1, 2004
Publication Date: March 7, 2005
Citation: Zeng, H., Briske-Anderson, M. 2005. Inhibitory effect of prolonged-butyrate treatment on migration and invasion of HT1080 tumor cells [abstract]. The Federation of American Societies for Experimental Biology Journal. 19(5):A1693. Technical Abstract: Butyrate, a normal constituent of the colonic luminal contents, has been hypothesized that butyrate may inhibit the invasion of tumor cells. The present study was to investigate the effects of butyrate on the growth, migration, and invasion characteristics of tumor HT1080 cells. HT1080 cells cultured in the presence of 0.5 and 1 mmol/L butyrate for 14 d exhibited an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, thus showing slower cell growth. Interestingly, 0.5 and 1 mmol/L butyrate inhibited the migration and invasion rate of the tumor cells when compared with the untreated cells. The protein and mRNA levels of the tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2 were significantly increased in HT1080 cells cultured with 0.5 and 1 mmol/L butyrate. Enzymatic activities and the mRNA level of the latent forms of matrix metalloproteinase (MMP), pro-MMP-2 and pro-MMP-9, were also increased in HT1080 cells cultured with 0.5 and 1 mmol/L butyrate. In contrast, the active MMP-2 was detectable by zymographic analysis in control but not butyrate conditioned media. Collectively, these results demonstrate that prolonged and low-dose butyrate treatment increases both pro-metastasis MMP-2, -9 and anti-metastasis TIMP-1, -2 expression, and the net effect of these increases is the inhibition of pro-MMP-2 activation and of tumor cell migration/invasion potential.