Influence of conjugated linoleic acid isomers on the metastasis of colon cancer cells in vitro and in vivo

Abstract

This study investigated the isomer-specific effects of cis-9, trans-11 ( c9, t11) and trans-10, cis-12 ( t10, c12) conjugated linoleic acid (CLA) on the metastasis of colon cancer cells in vitro and in vivo. Cell migration was examined by a Boyden chamber assay in SW480 cells. MMP-9 activity was monitored by gelatin zymography, and MMP-9 protein and mRNA levels were determined by Western blot and RT-PCR analysis, respectively, in SW480 cells. For the experimental metastasis, BALB/c mice were injected intravenously with CT-26 cells in the tail vein. Mice were fed a diet containing either no CLA or 0.1% c9, t11 or t10, c12 CLA for 4 weeks. In experimental metastasis, the numbers of pulmonary nodules were significantly lower in mice fed CLA isomers than in mice fed a control diet ( P<.05). Results from the Boyden chamber assay revealed that c9, t11 CLA significantly inhibited cell migration ( P<.05), whereas t10, c12 CLA had no effect on cell migration. The activity of MMP-9 was significantly inhibited by c9, t11 CLA ( P<.05) but not by t10, c12 CLA. However, neither MMP-9 protein nor mRNA levels were altered by either of these CLA isomers. We have demonstrated that diets containing 0.1% c9, t11 and t10, c12 CLA were equally effective in inhibiting colon cancer cell metastasis in vivo. However, in vitro, only c9, t11 but not t10, c12 inhibited colon cancer cell migration and MMP-9 activity.