Tributyrin emulsion as a potent inhibitor of serum- or heregulin-stimulated proliferation of colon cancer cells

Abstract

Blockade of the heregulin-mediated growth signaling is important to prevent the proliferation of colon cancer. We previously reported that butyrate is a potent inhibitor of the heregulin-stimulated proliferation of colon cancer cells. While clinical use of butyrate is limited due to its very short plasma half-life, using tributyrin (TB) as a prodrug of butyrate may be an alternative solution. In the present study, we investigated a possibility to use TB-incorporated emulsion as a potent inhibitor of colon cancer cell proliferation. When the growth of CaCo-2 and SNU-C4, two colon cancer cells, was stimulated by serum, TB emulsion exerted 2.8- and 5.7-fold higher inhibitory effect compared with free butyrate, based on the 50 % inhibitory concentration. When the growth of colon cancer cells was stimulated by heregulin, pretreatment with TB emulsion almost completely suppressed the heregulin-stimulated proliferation of cells at a concentration ineffective as butyrate. The more potent inhibition of heregulin-stimulated proliferation by TB emulsion was associated with more effective blockade of the activation of Akt and ERK1/2, which are important downstream molecules mediating hereuglin-stimulated proliferation of cancer cells. Taken together, TB emulsion is a potent agent that can inhibit the proliferation of colon cancer cells.