Des (1-3) IGF-I-stimulated growth of human stromal BPH cells is inhibited by a vitamin D3 analogue

Crescioli, Clara; Villari, Donata; Forti, Gianni; Ferruzzi, Pietro; Petrone, Luisa; Vannelli, G. B.; Adorini, Luciano; Salerno, R.; Serio, Mario; Maggi, Mario

doi:10.1016/s0303-7207(02)00370-2

Cited by 25 publications

(25 citation statements)

References 29 publications

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“…As previously reported (8,10,11), BPH cell proliferation was significantly increased (P , 0.01) by testosterone (156^8%), and GFs, such as Des(1-3)IGF-I (194^6%) or KGF (183^5%). When cell growth was stimulated for 48 h with testosterone or GFs (Fig.…”

Section: Resultssupporting

confidence: 83%

“…We have recently reported that a calcitriol analogue, analogue V or BXL-353, not only reduced the growth of human BPH cells, but also induced a death program by decreasing the expression of the survival factor bcl-2 (8). In addition, we found that BXL-353 completely blocked intra-prostatic growth factor (GF) or androgen-induced BPH cell proliferation, most probably by preventing GF receptor phosphorylation and disrupting androgen -GF cross-talk (8,10,11). In a model of testosterone-supplemented, orchidectomized rats, this analogue was able to counteract the growth-promoting activity of testosterone by decreasing prostate volume without affecting calcemia (11).…”

Section: Introductionmentioning

confidence: 83%

“…Thus, clusterin induction by BXL-628 treatment is consistent with the capacity of this compound to inhibit proliferation and induce apoptosis in prostate cells. The capacity to induce growth arrest and programmed death in prostate cells (8,10,11), even in malignant prostate cells (34), appears to be a common property of VDR ligands. These effects are unrelated to the presence of a functioning AR (34), but could depend on the ability of VDR ligands to interfere with GF receptor autophosphorylation (8).…”

Section: Discussionmentioning

confidence: 99%

“…Increasing concentrations (10 218 to 10 27 M) of calcitriol or BXL-628 with or without a fixed concentration of testosterone (10 nM), KGF or Des(1-3)IGF-I (10 ng/ml) were used. Growth assays were also carried out using a fixed concentration of androgens (10 nM) with or without BXL-628 (1 nM and 10 nM), the anti-androgens finasteride (1 nM) and Cyp (100 nM); using a fixed concentration of testosterone (10 nM) or GFs (10 ng/ml) with or without BXL-628 (10 nM).…”

Section: In Vitro Assaysmentioning

confidence: 99%

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Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia

Crescioli

Ferruzzi

Caporali

et al. 2004

European Journal of Endocrinology

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Objective: Calcitriol analogues might represent an interesting new therapy for benign prostate hyperplasia (BPH). We here report the preclinical characterization of BXL-628, an analogue selected for an ongoing double-blind, randomized, placebo-controlled phase II trial in BPH. Design: Experiments with BXL-628 were carried out in human BPH cells and in the ventral prostate of intact and castrated rats. Methods: BPH cell and rat prostate growth were evaluated along with morphological and biochemical hallmarks of apoptosis. Results: BXL-628 inhibited human BPH cell proliferation and induced apoptosis even in the presence of androgens or growth factors. It also decreased prostate growth to an extent similar to finasteride, inducing DNA fragmentation and apoptosis, both in intact and in testosterone-supplemented castrated rats. Accordingly, BXL-628, like finasteride, increased the expression of clusterin, a prostatic atrophy marker. However, BXL-628 did not inhibit 5a-reductase 1 and 2, did not bind to the androgen receptor (AR) in BPH homogenates and did not affect AR-coupled luciferase activity. In addition, BXL-628 did not affect rat pituitary and testis activity or calcemia. Conclusions: BXL-628 inhibited in vitro and in vivo prostate cell proliferation, and therefore might represent a novel, interesting option for the treatment of BPH.European Journal of Endocrinology 150 591-603

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Section: Resultssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Assaysmentioning

confidence: 99%

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Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia

Crescioli

Ferruzzi

Caporali

et al. 2004

European Journal of Endocrinology

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“…Benign prostate hyperplasia (BPH) is one of the most common conditions affecting men (24). It is a chronic progressive disease, histologically proven in approximately 50% of men over 50 years, and 90% of men who are 80 years of age (25).…”

Section: Discussionmentioning

confidence: 99%

Is vitamin D associated with testosterone in benign prostate hyperplasia?

Roussev

Gerova

Kosev

et al. 2017

SSM

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LUTS treatment: Future treatment options

2007

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Lower urinary tract symptoms (LUTS) are commonly divided into storage, voiding, and postmicturition symptoms, and may occur in both men and women. Male LUTS have historically been linked to benign prostatic hyperplasia (BPH), but are not necessarily prostate related. The focus of treatment for LUTS has thus shifted from the prostate to the bladder and other extraprostatic sites. LUTS include symptoms of the overactive bladder (OAB), which are often associated with detrusor overactivity. Treatment for LUTS suggestive of BPH has traditionally involved the use of alpha(1)-adrenoceptor (AR) antagonists; 5alpha-reductase inhibitors; and phytotherapy-however, several new therapeutic principles have shown promise. Selective beta(3)-adrenoceptor agonists and antimuscarinics are potentially useful agents for treating LUTS, particularly for storage symptoms secondary to outflow obstruction. Other agents of potential or actual importance are antagonists of P2X(3) receptors, botulinum toxin type A, endothelin (ET)-converting enzyme inhibitors, and drugs acting at vanilloid, angiotensin, and vitamin D(3) receptor sites. Drugs interfering with the nitric oxide/cGMP-cAMP pathway, Rho-kinase and COX inhibitors, as well as drugs targeting receptors and mechanisms within the CNS, are also of interest and deserving of further study for the treatment of LUTS.

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Des (1-3) IGF-I-stimulated growth of human stromal BPH cells is inhibited by a vitamin D3 analogue

Cited by 25 publications

References 29 publications

Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia

Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia

Is vitamin D associated with testosterone in benign prostate hyperplasia?

LUTS treatment: Future treatment options

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