PPARalpha agonists clofibrate and gemfibrozil inhibit cell growth, down-regulate hCG and up-regulate progesterone secretions in immortalized human trophoblast cells.
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.
Hashimoto
Fumie
F
Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado, Saitama 350-0295, Japan. hasimoto@josai.ac.jp
Oguchi
Yoshinobu
Y
Morita
Mieko
M
Matsuoka
Kikumi
K
Takeda
Satoru
S
Kimura
Masayuki
M
Hayashi
Hidenori
H
D000924:Anticholesteremic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D002994:Clofibrate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004347:Drug Interactions; D015248:Gemfibrozil / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020675:Peroxisomes / Q000502:physiology; D011374:Progesterone / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013347:Subcellular Fractions; D014157:Transcription Factors / Q000819:agonists*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000924:Anticholesteremic Agents; D006063:Chorionic Gonadotropin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011374:Progesterone; D007770:L-Lactate Dehydrogenase; D002994:Clofibrate; D015248:Gemfibrozil