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

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.

Effects of WY-14643 on Peroxisomal Enzyme Activity and Hormone Secretion in Immortalized Human Trophoblast Cells

“…Chance et al 32) reported that catalase activity in HepG2 cells was increased to about 1.4 times higher than the control value by 1.0 mM clofibric acid. In our results, the activity in trophoblast cells was increased to about 1.34 times the control value by 1.0 mM clofibric acid, 3) indicating that the sensitivity of catalase in trophoblast cells to clofibric acid is the same as that of human hepatocytes.…”

“…In the present study, proliferation (DNA and protein contents) was decreased to about 40 and 45% after 3 d in culture in the presence of 0.2 mM WY-14643 (Fig. 1) and 2.5 mM clofibric acid, 3) respectively. These results suggest that trophoblast cells are somewhat more susceptible to WY-14643 and clofibric acid than choriocarcinoma cells.…”

“…Catalase activity was increased by WY-14643 ( Fig. 1(1)), gemfibrozil, and clofibric acid 3) after incubation for 3 d. Furthermore, WY-14643 and gemfibrozil increased catalase activity at lower concentrations than clofibric acid. Therefore, we support the positive effect of rodent peroxisome proliferators on human cells.…”

“…3) In the preceding paper, we clarified that clofibric acid induces the proliferation of trophoblast cell microperoxisomes. 4) Rat liver cells are useful for experiment of peroxisomes, but they do not secrete hormone.…”

“…3) In the present experiment, the immortalized cells were cultured with or without WY-14643 for 3 d, and their DNA and protein contents were then determined. The DNA and protein contents of the control cells gradually increased during the incubation (data not shown), indicating the normal growth of the cells.…”