Simvastatin induces apoptosis and alters cytoskeleton in endometrial stromal cells.
BACKGROUND
Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase, with antimitotic, antioxidant, antiinflammatory, and immunomodulatory properties. Recent studies have shown that statins reduce the growth of human endometrial stromal (HES) cells and protect from the development of endometriosis in animal models.


OBJECTIVE
The present study was conducted to evaluate the effects of simvastatin on apoptosis and cytoskeleton of HES cells.


METHODS
In vitro experiments were performed in the university research laboratory.


METHODS
HES cells were obtained from endometrial biopsies collected from nine subjects in the proliferative phase of their menstrual cycle.


METHODS
The effect of simvastatin (10 and 30 mum) and/or geranylgeranyl pyrophosphate (GGPP, 30 mum) on caspase 3 and 7 activity, DNA fragmentation, and HES cell morphology was evaluated.


RESULTS
Simvastatin induced significant time- and concentration-dependent apoptotic effects on HES cells as determined by increased activity of executioner caspases and DNA fragmentation. Simvastatin also caused profound alterations in HES cell morphology and F-actin cytoskeleton. This effect was abrogated by geranylgeranyl pyrophosphate, an important product of the mevalonate pathway.


CONCLUSIONS
Simvastatin induces apoptosis and disruption of the cytoskeleton of HES cells by reducing isoprenylation in cultures of human endometrial stroma. The present findings may lead to the development of novel treatments for endometriosis involving statins.
Sokalska
Anna
A
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of California Davis, Sacramento, CA 95817, USA.
Wong
Donna H
DH
Cress
Amanda
A
Piotrowski
Piotr C
PC
Rzepczynska
Izabela
I
Villanueva
Jesus
J
Duleba
Antoni J
AJ
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D048430:Cell Shape; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D053148:Caspase 3; D053179:Caspase 7