Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms—action of two new agents

Kumar, Rajeev; Verma, Vikas; Sarswat, Amit; Maikhuri, Jagdamba P.; Jain, Ashish; Jain, Rajeev; Sharma, Vikas; Dalela, Divakar; Gupta, Gopal

doi:10.1007/s10637-010-9620-2

Cited by 32 publications

(27 citation statements)

References 60 publications

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“…In vivo models of BPH suggest that androgens and estrogens may act in synergy to induce prostate growth (Coffey and Walsh, 1990; Kumar et al, 2012). Estrogens mediate their effects via estrogen receptors; the subtype estrogen receptor alpha (ERα) is necessary for induction of prostate proliferation with estradiol and is considered a key mediator of prostatic epithelial proliferation (Risbridger et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Selective estrogen receptor modulators (SERMs) are a promising new treatment strategy for targeting estrogen pathways implicated in BPH. A recent report indicates that SERMs in combination with 5ARI may be particularly promising for decreasing prostate cell proliferation in BPH (Kumar et al, 2012). Therefore, a better understanding of the localization and relative quantification of ERα expression may be helpful in selecting compounds to target ERα signaling in the prostate.…”

Section: Introductionmentioning

confidence: 99%

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Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

et al. 2013

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Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goal of this study was to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR & ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR & ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

et al. 2013

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“…In BPH, an important role is played by hormonal imbalance; in fact, the development and the growth of the prostate is controlled by a synergy of normal levels of androgens and estrogens [25] and, consequently, by a controlled balance between cell growth and apoptosis [16]. …”

Section: Endocrine Control Of Prostatic Growthmentioning

confidence: 99%

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

Minutoli

Rinaldi

Marini

et al. 2016

IJMS

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Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

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“…Normal levels of androgens and oestrogens synergistically maintain the prostate (Kumar et al, 2012). The prostate is also a target tissue for oestrogens.…”

Section: Introductionmentioning

confidence: 99%

The therapeutic effects of WSY-0702 on benign prostatic hyperplasia in RWPE- 1

Oh¹,

Kwon²,

Hwang³

et al. 2017

TANG [HUMANITAS MEDICINE]

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Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in older men. WSY-0702 is the extracted from the traditional medicinal plant; Seoritae, and it has effects of anti-obesity, chronic cervical pain, and anti-oxidant. The present study aimed to investigate the therapeutic potential of WSY-0702 in the prevention and treatment of BPH. Several parameters including inflammatory mediators, hormones, and oxidative stress (OS) have been considered to play a role in the development of BPH. Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. An in vitro study showed that proliferation inhibited the human prostate epithelial cell line RWPE-1 in a dose-dependent manner. In cell line, the cell cycle at the G2/M and G0/G1 phase and downregulated the expression of CyclineB1 (CCNB1) and CyclineD1 (CCND1). In addition, we measured the H 2 O 2 -induced OS damage using RWPE-1 cells. We examined the relative expression of protein involved in the regulation of prostate apoptosis: transforming growth factor (TGF)-β, a negative growth factor able to induced prostate apoptosis under physiological conditions. These results suggest that WSY-0702 that can inhibit the growth of prostate epithelial cell by a mechanism that may involve arresting the cell cycle and downregulating CCNB1 and CCND1 expression. In addition, WSY-0702 exposure resulted in significant protective effects in H 2 O 2 -stressed PWPE-1 cells by reduction in TGF-β levels.

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Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms—action of two new agents

Cited by 32 publications

References 60 publications

Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

The therapeutic effects of WSY-0702 on benign prostatic hyperplasia in RWPE- 1

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