Statins Inhibit Growth of Human Endometrial Stromal Cells Independently of Cholesterol Availability1

Piotr C Piotrowski, Piotr Piotrowski, Kwintkiewicz J, Jakub Kwintkiewicz, Rzepczynska IJ, Izabela J. Rzepczynska, Yasemin Seval, Seval Y, Hakan Çakmak, Cakmak H, Hakan Cakmak, Aydın Arıcı, Aydin Arici, Arici A, Antoni J Duleba, Duleba AJ, Antoni J. Dulęba
Biology of reproduction · 2006 · vol. 75(1) , pp. 107–111 · doi:10.1095/biolreprod.106.051763 · PMID:16571871 · W2147203397
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Statins inhibited human endometrial stromal cell proliferation and MAPK3/1 phosphorylation, independently of cholesterol levels, with mevalonate but not squalene reversing the inhibitory effects.

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Abstract

Endometriosis is characterized by ectopic growth of endometrial tissues. Statins, inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), have been shown to decrease proliferation of several mesenchymal tissues. Actions of statins may be related to decreased availability of cholesterol as well as intermediate metabolites of the mevalonate pathway downstream of HMGCR. This study was designed to evaluate effects of statins on growth of endometrial stromal cells and to investigate mechanisms of these effects. Human endometrial stromal cells were cultured in the absence and in the presence of serum and with or without mevastatin and simvastatin. DNA synthesis and viable cell numbers were determined. Effects of statins were also evaluated in the presence of mevalonate and squalene. Furthermore, effects on phosphorylation of mitogen-activated protein kinase 3/1 (MAPK3/1) (also known as extracellular signal-regulated kinase [ERK1/2]) were determined. Mevastatin and simvastatin induced a concentration-dependent inhibition of DNA synthesis and viable cell count in chemically defined media and in the presence of serum. Mevalonate, but not squalene, abrogated inhibitory effects of statins on cell proliferation. Statins inhibited MAPK3/1 phosphorylation. This is the first study demonstrating that statins inhibit growth of endometrial stromal cells. This effect is also demonstrable in the presence of a supply of cholesterol and may be related to decreased activation of MAPK3/1. The present observations may be relevant to potential therapeutic use of statins in conditions such as endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometrium Hydroxymethylglutaryl-CoA Reductase Inhibitors Cell Proliferation Cell Proliferation Endometrium Endometrium Endometrium Female Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors Hydroxymethylglutaryl-CoA Reductase Inhibitors Mevalonic Acid Mevalonic Acid Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase 3 Phosphorylation Squalene Squalene

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