Tributyrin induces growth inhibitory and differentiating effects on HT-29 colon cancer cells in vitro.
Tributyrin (TB) is a prodrug of butyrate known to induce tumor cells to differentiate. We examined its effects on cell growth, viability, cellular morphology and differentiation of HT-29 colon cancer cells in vitro, as reflected by the expression of CEA, E-cadherin and the induction of alkaline phosphatase activity. TB, applied in a stable emulsion, inhibited tumor cell proliferation in a reversible and dose-dependent manner (0.5-4 mM) with significant morphological changes. The IC50 value of TB was 1 mM after 6 days. For comparison, sodium butyrate, applied in equimolar concentration, inhibited cell growth with an IC50 value of 2.2 mM. TB treatment at concentrations of 0.5 mM and 2 mM resulted in an increase of the doubling times by 18% and 160%, respectively, without any effects on cell viability. By a colorimetric immunoassay, 1.5 mM TB induced the expression of both CEA and E-cadherin by about 260% and 100%, respectively. Furthermore, the activity of the brush border enzyme alkaline phosphatase was enhanced in a dose-dependent manner, up to 60-fold at the maximum of 2 mM TB. Our results show that TB is more active than butyrate in suppressing cell growth and concomitantly promoting differentiation of HT-29 colon cancer cells. Hence it may be a promising candidate for clinical therapeutic protocols and merits further investigation.
Schröder
C
C
Institut fur Pharmazie der Freien Universitat Berlin, Germany.
Eckert
K
K
Maurer
H R
HR
D000469:Alkaline Phosphatase / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D014280:Triglycerides / Q000494:pharmacology*
D002087:Butyrates; D015820:Cadherins; D002272:Carcinoembryonic Antigen; D006131:Growth Inhibitors; D014280:Triglycerides; D000469:Alkaline Phosphatase; C005830:tributyrin