Article

PPARalpha agonists clofibrate and gemfibrozil inhibit cell growth, down-regulate hCG and up-regulate progesterone secretions in immortalized human trophoblast cells.

Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado, Saitama 350-0295, Japan.
Biochemical Pharmacology (impact factor: 4.7). 07/2004; 68(2):313-21. DOI:10.1016/j.bcp.2004.03.024 pp.313-21
Source: PubMed

ABSTRACT We studied effects of PPARalpha agonists clofibric acid and gemfibrozil on cell growth and functions of immortalized human extravillous trophoblast cells. Levels of DNA and protein gradually increased during incubation for 4 days. Gemfibrozil (>0.25mM) and clofibric acid (2.5mM) suppressed the rate of increase in DNA and protein. Specific activities of fatty acyl-CoA oxidase and catalase were increased to about 1.2-2.0 times the control value by 0.05mM gemfibrozil and 1.0 and 2.5mM clofibric acid after incubation for 3 days. Acid phosphatase activity showed a small increase in response to both agents, but esterase activity changed little. The secretion of progesterone from the cells into the medium was increased by 0.25mM gemfibrozil and 1.0 and 2.5mM clofibric acid after incubation for 3 days, but that of human chorionic gonadotropin (hCG) was decreased by 0.35mM gemfibrozil and 2.5mM clofibric acid. The specific activity of lactate dehydrogenase in the cells was hardly changed at all after incubation for 3 days. These results suggest that gemfibrozil and clofibric acid inhibit the proliferation of trophoblast cells. Cell metabolism is probably affected by both agents. The two agents may down-regulate hCG and up-regulate progesterone secretions.

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Keywords

0.05mM gemfibrozil
 
0.25mM gemfibrozil
 
0.35mM gemfibrozil
 
2.5mM clofibric acid
 
4 days
 
Acid phosphatase activity
 
cell growth
 
Cell metabolism
 
clofibric acid
 
control value
 
esterase activity
 
fatty acyl-CoA oxidase
 
human chorionic gonadotropin
 
immortalized human extravillous trophoblast cells
 
PPARalpha agonists clofibric acid
 
Specific activities
 
specific activity
 
trophoblast cells
 
two agents
 
up-regulate progesterone secretions