Simvastatin Induces Apoptosis and Alters Cytoskeleton in Endometrial Stromal Cells

Sokalska, Anna; Wong, Donna H.; Cress, Amanda B.; Piotrowski, Piotr; Rzepczynska, Izabela J.; Villanueva, Jesus A.; Dulęba, Antoni J.

doi:10.1210/jc.2010-0072

Cited by 43 publications

(45 citation statements)

References 33 publications

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“…22 The proposed mechanisms of actions of statins on endometriosis implants are stimulation of apoptosis, inhibition of endometrial cell proliferation, blockage of angiogenesis, disruption of adherence and invasion of endometrial cells to peritoneum, and decrease in oxidative stress and inflammation. 10,[22][23][24][25][26] Decreased sensitivity of endometrial tissue to spontaneous apoptosis contributes to the implantation and growth of endometrium at ectopic sites. 27 Ectopic endometriosis implants demonstrate high ERK1/2 signaling pathway activity resulting in enhanced cell survival.…”

Section: Discussionmentioning

confidence: 99%

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

et al. 2012

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Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.

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Section: Discussionmentioning

confidence: 99%

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

et al. 2012

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“…In vitro cultures of hESCs to which simvastatin was added have displayed a statistically significant, dose-dependent reduction in the number of viable cells and cell adhesion as well as increased apoptosis (25,26). Altered cell morphology related to the F-actin cytoskeleton also was a consistent finding, which can be associated with impaired cell adhesion and motility.…”

Section: Statinsmentioning

confidence: 90%

Pharmacologic therapies in endometriosis: a systematic review

Soares¹,

Martínez-Varea

Hidalgo-Mora

et al. 2012

Fertility and Sterility

138

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“…85 All these effects were abrogated by GGPP, indicating that simvastatin induced apoptosis by inhibition of geranylgeranylation.…”

Section: Statins In Treatment Of Endometriosismentioning

confidence: 97%

“…84 Our recent study has demonstrated that simvastatin profoundly alters endometrial stromal cell and cytoskeleton morphology, disrupting F-actin fibers. 85 Another likely target of action of statins pertains to their effects on invasiveness of endometriotic cells. Invasiveness may be affected by MMPs leading to local destruction of the ECM and consequent establishment of the disease.…”

Section: Statins In Treatment Of Endometriosismentioning

confidence: 99%

Novel Therapies Targeting Endometriosis

et al. 2011

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Endometriosis is an often painful disorder in which the endometrial glands and stroma grow outside the uterus. The disease affects women's quality of life and is a common cause of infertility. In this review, we describe promising new developments in the field based on in vitro assays and rodent models, each of which has the potential to be beneficial in the treatment of this disease. We will specifically describe the role of anti-inflammatory drugs, selective estrogen, or progesterone modulators, statins, antiangiogenic agents, and the potential for targeting stem cells as likely methods to hone in and eliminate endometriosis. The most promising of these potential therapies are currently slated for further testing in both rodent and nonhuman primate trials.

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Simvastatin Induces Apoptosis and Alters Cytoskeleton in Endometrial Stromal Cells

Abstract: 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.

Cited by 43 publications

References 33 publications

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

Pharmacologic therapies in endometriosis: a systematic review

Novel Therapies Targeting Endometriosis

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