Transforming growth factor β1 transduced mouse prostate reconstitutions: II. Induction of apoptosis by doxazosin

Yang, Guang; Timme, Terry L.; Park, Sang Hee; Wu, Xiuyin; Wyllie, Michael G.; Thompson, Timothy C.

doi:10.1002/(sici)1097-0045(19971101)33:3<157::aid-pros2>3.0.co;2-g

Cited by 64 publications

(44 citation statements)

References 18 publications

(22 reference statements)

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“…Support for this notion stems from observations in the mouse in which doxazosin treatment induced apoptosis in prostate reconstitutions but did not affect the glandular epithelia of the ventral prostate of the engrafted mice. 14 The FGF family members are mitogenic to both prostatic epithelial and stromal cells. 39 bFGF is produced mainly by stromal and, to a lesser extent, by epithelial cells 36,40 and participates in prostate growth regulation through an autocrine effect on stromal cells and a weak paracrine effect on epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 In vivo 1-ADR blockade in either man or rats result in decreased smooth muscle myosin heavy chain gene expression. 13 Prostatic cell apoptosis has been identified as an additional mechanism of long term action for doxazosin and terazosin, [14][15][16][17] while it has been postulated that the apoptotic effect is probably quinazoline nucleus directed rather than 1-ADR mediated. 18 The apoptotic effect of 1-ADR antagonists has been attributed to transforming growth factor ß1 (TGF-ß1) since in vitro treatment of primary human prostate cell cultures with doxazosin 19 , as well as in vivo treatment with terazosin 20 , resulted in enhanced TGF-ß1 expression.…”

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confidence: 99%

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Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Mitropoulos

Kyroudi-Voulgari²,

Christelli³

et al. 2009

CIM

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Purpose: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. Methods: Wistar rats were treated with terazosin (1.2 mg/ kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. Results: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the antibFGF antibody. In contrast, the same staining in terazosintreated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. Conclusions: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis.Drugs that block the action of sympathetic neurotransmitters on 1-adrenergic receptors ( 1-ADRs) are widely used for the treatment of patients with benign prostate hyperplasia (BPH)-related lower urinary tract symptoms. The rationale for their use stems is that they effectively relax prostate smooth muscles, 1 which represent approximately 40% of the cellular volume in hyperplastic glands. 2 The biological effects of extrinsic factors such as hormones and other endocrine-related agents on the prostate are mediated by various peptide growth factors produced by the gland and influence prostate growth, differentiation and function by promoting inter-and intracellular signaling between and within cell populations, through paracrine, autocrine and intracrine effects. 3 Data from several studies indicate that 1-ADR antagonists may not act solely on smooth muscle contractility. Intact autonomic innervation of the rat ventral prostate is necessary to maintain its structural and functional integrity. [4][5][6] Administration of the sympathomimetic phenylephrine induces ventral prostate hyperplasia associated with reduced rates of cellular apoptosis, but not with increased rates of cellular proliferation. 7 Moreover, rapid proliferation of prostatic epithelial cells has been seen in the spontaneously hypertensive rat, 8 an animal model with in-ORIGINAL RESEARCH

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Mitropoulos

Kyroudi-Voulgari²,

Christelli³

et al. 2009

CIM

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“…Our initial clinical observations were in full accord with experimental studies using a mouse model of prostate hyperplasia, in which doxazosin exhibited a potent apoptotic effect against oncogene-induced prostatic growth. 34 In the androgen-independent prostate cancer cells, PC-3 and DU-145 pharmacologically relevant doses of the quinazoline-derived a 1 -antagonists, doxazosin and terazosin (15 -25 mM) resulted in significant induction of apoptosis in vitro. 33 In contrast, tamsulosin, a methoxysulphonamide derived a 1 -adrenoceptor antagonist had no effect on prostate growth.…”

Section: Discussionmentioning

confidence: 99%

Induction of prostate apoptosis by α1-adrenoceptor antagonists: mechanistic significance of the quinazoline component

Anglin

Glassman

Kyprianou

2002

Prostate Cancer Prostatic Dis

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a 1 -Adrenoceptor antagonists, have been documented to induce apoptosis and reduce prostate tumor vascularity in benign and malignant prostate cells. The quinazoline based a 1 -antagonists, doxazosin and terazosin but not tamsulosin (a sulphonamide derivative) suppress prostate growth without affecting cell proliferation. These quinazoline-mediated apoptotic effects occur via an a 1 -adrenoceptor independent mechanism potentially involving activation of the TGF-b signal transduction pathway. This review discusses the current knowledge of the action of quinazoline-derived a 1 -adrenoceptor antagonists in the benign and malignant prostate and their potential therapeutic use in the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Finally, a molecular pathway is proposed for their observed apoptotic function against prostate cells. Increased understanding of the action of these established and clinically accepted agents would provide a basis for the design of safe, effective therapeutic regimens in the treatment of prostatic diseases.

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“…Several studies in mice suggest that treatment with quinazoline-derived α 1 -AR antagonists, doxazosin and terazosin, which are long-lasting drugs used to provide acute relief of the obstructive symptoms, also reduce tumor growth [445]. The in vivo mechanism(s) is(are) not clear, however, culturing prostate cells with α 1 -AR antagonist reduces cellular proliferation and increases the rate of apoptosis [445,446] via an α 1 -AR independent mechanism [447]. Sympathetic activation may also regulate prostate cancer progression via β-AR-mediated mechanisms.…”

Section: Sns and Tumor Growthmentioning

confidence: 99%

Sympathetic modulation of immunity: Relevance to disease

Bellinger

Millar

Perez

et al. 2008

Cellular Immunology

225

185

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Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease-or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.

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Transforming growth factor β1 transduced mouse prostate reconstitutions: II. Induction of apoptosis by doxazosin

Cited by 64 publications

References 18 publications

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Induction of prostate apoptosis by α1-adrenoceptor antagonists: mechanistic significance of the quinazoline component

Sympathetic modulation of immunity: Relevance to disease

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