Selective estrogen receptor modulators (SERMS)

Díez-Pérez, Adolfo

doi:10.1590/s0004-27302006000400017

Cited by 21 publications

(15 citation statements)

References 150 publications

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“…These effects depend on ERs and co-regulators expressed among the different tissue types, the ER-modulated genes, and activation of membrane cytoplasmic signals. Raloxifene (RAL) is a SERM that has been reported to be a mixed estrogen agonist/antagonist (Kim et al, 2002a;Diez-Perez, 2006) and has been demonstrated to be a safe agent for the prevention of breast cancer and female and male osteoporosis (Smith, 2005(Smith, , 2006. RAL binds ERa with a higher affinity than ERb (Kim et al, 2002a,b;Zeng et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β

Rossi

Bellastella

Rosa

et al. 2011

Journal Cellular Physiology

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Raloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen-dependent and -independent prostate cell (PC) lines via activation of ERβ and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen-dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERβ and lacked ERα. In EPN cells, there was an increase in the pre-G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment; bcl-2 mRNA and Bcl-2 protein levels were significantly reduced, while activated caspase-3 and Par-4 levels increased significantly after either E2 or RAL treatment; in addition, c-myc transcript was inhibited after 10(-6) M RAL treatment. A dose-dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase-3 activation and Par-4 increase after either E2 or RAL treatment; while c-myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell-specific, depending on ERβ or ERβ/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non-genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression.

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Section: Introductionmentioning

confidence: 99%

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β

Rossi

Bellastella

Rosa

et al. 2011

Journal Cellular Physiology

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“…However, primary or secondary antiestrogen resistance is well known in laboratory and clinical settings 13,14. Further, selective estrogen receptor modulators (SERM) have been introduced, some of which like fulvestrant, are being used in clinical practice 15,16. SERMs and estrogen depletion by aromatase inhibitors have been shown to overcome tamoxifen resistance17,18 at least in part and temporarily.…”

Section: Introductionmentioning

confidence: 99%

Effects of Celecoxib and Ly117018 Combination on Human Breast Cancer Cells in Vitro

Baumann

Klusmeier

Eggemann

et al. 2009

Breast Cancer�(Auckl)

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Activation and signalling of estrogen receptor (ER) and COX-2 represent two important pathways in breast cancer cell regulation. Activation of either pathway is associated with breast cancer cell proliferation and eventually malignant progression. Raloxifene analogue, Ly117018, a selective estrogen receptor modulator and celecoxib, a specifi c COX-2 inhibitor have been shown to inhibit breast cancer cell proliferation when used alone in vitro and in vivo. In this study, the combined drug effects on hormone-dependent MCF-7 and hormone-independent MDA-MB-435 cells in vitro were evaluated. Cell proliferation assays excluded drug antagonism and revealed a moderate synergistic growth inhibitory activity of Ly117018 and celecoxib on both cell lines when combined in specifi c concentrations. Growth inhibition of either compound was not associated with cell cycle arrest. In MCF-7 cells, western blot analysis revealed a decreased phosphorylation of the AKT protein by either agent alone or in combination. In MDA-MB-435 cells, celecoxib alone induced an increase in AKT phosphorylation relative to total AKT protein; this effect was decreased in the presence of Ly117018. These results indicate that these two drugs are non-antagonistic; and when combined in specifi c concentrations, moderate synergistic antiproliferative activity of celecoxib and Ly117018 were observed in hormone-dependent MCF-7 and hormoneindependent MDA-MB-435 cells associated with changes in cell cycle distribution and regulation of AKT protein and phosphorylation. These fi ndings further support a central role of the ER-and COX-2 pathways in human breast cancer cells.

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“…antagonists (Diez-Perez 2006). Unfortunately, in postmenopausal women who take TAM the risk of developing endometrial cancer increases (Jordan 2008).…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor subtype-specific effects on markers of bone homeostasis

Hertrampf

Schleipen

Velders

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: Hertrampf, T., Schleipen, B., Velders, M., Laudenbach, U., Fritzemeier, K.H., Diel, P., Estrogen receptor subtype-specific effects on markers of bone homeostasis, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractTo further elucidate the processes involved in the physiology of bone-protection by estrogens, ovariectomized (OVX) rats were treated subcutaneously with 17-estradiol, the ER-specific agonist (16-LE2) and the ER-specific agonist (8-VE2).OVX and intact animals served as controls. Biomarkers of bone-formation (osteocalcin (OC), osteopontin (OPN)) and bone-resorption (telopeptides of collagen type I (CTx), pyridinoline cross-links (Pyd)) were quantified. Bone mineral density was measured by computed tomography.OVX-induced bone loss could be antagonized by subcutaneous administration of 17-estradiol and 16-LE2. Serum levels of CTx, OC and OPN were significantly elevated in OVX compared to intact animals and reduced by 17-estradiol and 16-LE2. Treatment of OVX rats with 8-VE2 did not affect BMD or bone-marker serum levels.Taken together, the complex expression pattern of bone-markers in OVX rats following subcutaneous administration of ER subtype-specific agonists indicates that 17-estradiol exerts its bone-protective effects by modulating the activity of osteoclasts and osteoblasts via ERα.

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Selective estrogen receptor modulators (SERMS)

Cited by 21 publications

References 150 publications

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β

Effects of Celecoxib and Ly117018 Combination on Human Breast Cancer Cells in Vitro

Estrogen receptor subtype-specific effects on markers of bone homeostasis

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