Tributyrin-induced differentiation promotes apoptosis of LS 174T colon cancer cells in vitro.
Tributyrin (glyceryl tributyrate, TB) is known to induce malignant cells to differentiate followed by arrest of cell growth and death via apoptosis. We investigated the effects of TB on the distribution of cell cycle phases, differentiation as measured by alkaline phosphatase activity (ALP), and apoptosis of LS 174T colon cancer cells expressed by morphological changes, externalization of phosphatidylserine and stimulation of various caspases. TB (0.6 mM) reduced the proliferation by a 5-fold decrease of tumor cells in the S-phase and 1.3-fold increase in the G2/M-phase of cell cycle after 24 h of incubation. The ALP activity was enhanced in a dose-dependent manner up to 180-fold by 1 mM TB. Apoptosis was seen only above 0.6 mM TB (5-fold increase). Studies with caspase inhibitors revealed that TB mediated cell death was linked to up-regulation of caspases 3 and 8. Our results indicate that TB-induced differentiation promotes apoptosis in LS 174T cells and may explain the mode of action of TB finally resulting in an arrest of tumor cell growth.
Schröder
Claudia P
CP
Institut fur Pharmazie der Freien Universitat Berlin, Abteilung fur Pharmazeutische Biochemie, Biotechnologie und Molekularbiologie, Berlin, Germany.
Maurer
H Rainer
HR
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D014280:Triglycerides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D014280:Triglycerides; D000469:Alkaline Phosphatase; D020169:Caspases; C005830:tributyrin