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>3.3.co;2-h

Cited by 10 publications

(17 citation statements)

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“…Recently, Dox has also been demonstrated to inhibit prostate growth by inducing apoptosis in stromal and epithelial cells, showing additional effects on long-term BPH treatment and emerging as a potential drug for the prevention and treatment of androgen-independent PCa (Yang et al 1997;Kyprianou et al 1998;Kyprianou and Jacobs 2000;Anglin et al 2002;Kyprianou 2003;Chiang et al 2005).…”

Section: Introductionmentioning

confidence: 99%

“…The induction of apoptosis by Dox on prostate cells has been attributed to an increased expression of transforming growth factor (TGF)-beta 1 (Yang et al 1997;Ilio et al 2001;Glassman et al 2001;Partin et al 2003). TGF-beta 1 is a multifunctional cytokine that regulates extracellular matrix production and degradation, differentiation, cell proliferation, and apoptosis (Huang and Lee 2003;Zhu and Kyprianou 2005;Fleisch et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes

2008

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We investigated the effects of doxazosin (Dox), an alpha-adrenoceptor antagonist used clinically for the treatment of benign prostatic hyperplasia (BPH), on the rat prostatic complex by assessing structural parameters, collagen fiber content, cell proliferation, and apoptosis. Adult Wistar rats were treated with Dox (25 mg/kg per day), and the ventral (VP), dorsolateral, and anterior prostate (AP) regions of the prostate complex were excised at 3, 7, and 30 days after treatment. At 24 h before being killed, the rats were injected once with 5-bromodeoxyuridine (BrdU; thymidine analog) to label mitotically active cells. The prostates were weighed and processed for histochemistry, morphometry-stereology, immunohistochemistry for BrdU, Western blotting for proliferating cell nuclear antigen (PCNA), and the TUNEL reaction for apoptosis. Dox-treated prostate lobes at day 3 presented increased weight, an enlarged ductal lumen, low cubical epithelial cells, reduced epithelial folds, and stretched smooth muscle cells. However, at day 30, the prostates exhibited a weight reduction of approximately 20% and an increased area of collagen and reticular fibers in the stromal space. Dox also reduced epithelial cell proliferation and increased apoptosis in the three prostatic lobes. Western blotting for PCNA confirmed the reduction of cell proliferation by Dox, with the AP and VP being more affected than the dorsal prostate. Thus, Dox treatment alters epithelial cell behavior and prostatic tissue mechanical demand, inducing tissue remodeling in which collagen fibers assume a major role.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes

2008

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“…The quilinazole-based class of α-adrenoceptor blockers, such as doxazosin, has the additional effect of inducing apoptosis of prostate cells, which has been demonstrated to be involved in the long-term efficacy of treatments for BPH (Anglin et al, 2002;Chiang et al, 2005;Kyprianou, 2003;Kyprianou et al, 1998;Yang et al, 1997). The induction of apoptosis in prostate cells by doxazosin has been attributed to an increased expression of TGF beta-1 (Glassman et al, 2001;Ilio et al, 2001;Partin et al, 2003;Yang et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…The induction of apoptosis in prostate cells by doxazosin has been attributed to an increased expression of TGF beta-1 (Glassman et al, 2001;Ilio et al, 2001;Partin et al, 2003;Yang et al, 1997). However, Zhao et al (2005), using a molecular approach, showed an involvement of TNFalpha in the doxazosin molecular mechanism of action and disproved the participation of the TGF-beta 1 pathway in doxazosin-induced apoptosis in stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Fibrosis-related gene expression in the prostate is modulated by doxazosin treatment

et al. 2012

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Our data suggest that relaxation of smooth muscle cells by alpha-blockers interferes with the mechanical dynamics of the prostatic stroma extracellular matrix components, generating a pro-fibrotic effect probably via the TGF-beta 1 signaling pathway. Long term treatment with doxazosin may also lead to a reduced turnover of extracellular matrix components. Our results add to a better understanding of the molecular mechanisms behind the effects of alpha-blockade on prostatic histoarchitecture and the response to treatment for benign prostatic hyperplasia.

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“…However, recent evidence demonstrates that cellular apoptosis may play a role. First in mice [39] and recently in humans [40], doxazosin has been shown to induce prostate apoptosis, particularly targeted at the smooth muscle component of the prostatic stroma. Apoptosis occurred following 3 months of doxazosin use [40].…”

Section: Cellular Response To ␣-Blockadementioning

confidence: 99%

α-Blockers: An effective treatment for prostatitis?

Caropreso

Moon

2000

Curr Urol Rep

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Chronic prostatitis is a multifaceted problem affecting men that is both poorly understood and poorly treated. It is inevitable, therefore, that no single treatment will benefit all patients. However, data suggest that some patients' problems can be treated effectively with alpha-blockers. The prostate is rich in alpha-adrenergic receptors, and some urodynamic studies have shown a failure of the bladder neck to relax during voiding. Other studies have demonstrated turbulent flow in the prostate leading to prostatic duct reflux. Because urine is acidic, reflux into the prostatic ducts will cause inflammation and pain. Thus alpha-blockers are an effective treatment for men with prostatitis caused by dysfunctional voiding.

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

Cited by 10 publications

References 0 publications

Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes

Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes

Fibrosis-related gene expression in the prostate is modulated by doxazosin treatment

α-Blockers: An effective treatment for prostatitis?

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