Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis

Liou, Shu Fen; Lin, Hung Hong; Liang, Jyh Chong; Chen, Ing Jun; Yeh, Jwu‐Lai

doi:10.1016/j.tox.2008.10.025

Cited by 30 publications

(25 citation statements)

References 37 publications

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“…However, it should be underlined that in PBA pretreated cells A175, at both doses, is less effective in comparison to cells not previously exposed to the inhibitor (proliferation rate in plus vs minus PBA are 16% vs 20.1% and 26.7% vs 37.5% for A175 25 and 50 μM respectively) and looses the dose-response effect. Similarly to our findings, PBA pretreatment also fails to fully counteract the action of other alpha1-AR blockers when given at concentrations higher than 10 μM [9,25]. Hence, it is possible either that other pretreatment conditions (higher PBA concentrations and/or longer pretreatments) would give different results, or that at least part of A175 action on cell proliferation does not involve alpha1D-AR binding.…”

Section: Discussionsupporting

confidence: 81%

“…However, doxazosin, terazosin, as well as naftopidil and its related compounds, reduce the growth rate also of DU145 and LNCaP cells [26,27,29], which, as previously discussed, lack alpha1D-ARs. It might be possible that all these compounds act either by interacting with other AR subtypes, or through an AR-independent mechanism, as suggested by many authors [9,18,25,28].…”

Section: Discussionmentioning

confidence: 99%

“…Similar to noradrenaline [11,25], the alpha1-AR agonist phenylephrine (Phe) has a direct mitogenic effect on PC3 growth (about 130% over controls). A175 dose-dependently inhibits Phe-stimulated cell proliferation, supporting the alpha1D-AR-mediated action of the compound.…”

Section: Discussionmentioning

confidence: 99%

“…The recent intense research has clearly shown that PC growth is reduced both "in vitro" and "in vivo" by some alpha1A/D-AR antagonists (labedipinedilol-A, [25]), or slightly alpha1D-vs.…”

Section: Introductionmentioning

confidence: 99%

“…Also the correlation between alpha1-AR antagonism and control of PC cells proliferation has not yet been completely elucidated and different action mechanisms have been demonstrated or suggested. The antiproliferative effect of naftopidil and of doxazosin seems to be alpha1-AR independent [9,[18][19][20]28], while evidences have been provided that the antitumor activity is alpha1-AR mediated in the case of labedipinediol-A [25] as well as of recently reported indolic analogues of naftopidil [29] and of the gemdiphenyldioxane derivatives [30,31].…”

Section: Introductionmentioning

confidence: 99%

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A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility “in vitro”

Colciago

Mornati

Ferri

et al. 2016

Pharmacological Research

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The progression of prostate cancer (PC) to a metastatic hormone refractory disease is the major contributor to the overall cancer mortality in men, mainly because the conventional therapies are generally ineffective at this stage. Thus, other therapeutic options are needed as alternatives or in addition to the classic approaches to prevent or delay tumor progression. Catecholamines participate to the control of prostate cell functions by the activation of alpha1-adrenoreceptors (alpha1-AR) and increased sympathetic activity has been linked to PC development and evolution. Molecular and pharmacological studies identified three alpha1-AR subtypes (A, B and D), which differ in tissue distribution, cell signaling, pharmacology and physiological role. Within the prostate, alpha1A-ARs mainly control stromal cell functions, while alpha1B-and alpha1D-subtypes seem to modulate glandular epithelial cell growth. The possible direct contribution of alpha1D-ARs in tumor biology is supported by their overexpression in PC. The studies here presented investigate the "in vitro"antitumor action of A175, a selective alpha1D-AR antagonist we have recently obtained by modifying the potent, but not subtype-selective alpha1-AR antagonist (S)-WB4101, in the hormone-refractory PC3 and DU145 PC cell lines. The results indicate that A175 has an alpha1D-AR-mediated significant and dose-dependent antiproliferative action that possibly involves the induction of G0/G1 cell cycle arrest, but not apoptosis. In addition, A175 reduces cell migration and adhesiveness to culture plates. In conclusion, our work clarified some cellular aspects promoted by alpha1D-AR activity modulation and supports a further pharmacological approach in the cure of hormone-refractory PC, by targeting specifically this AR subtype.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The recent intense research has clearly shown that PC growth is reduced both "in vitro" and "in vivo" by some alpha1A/D-AR antagonists (labedipinedilol-A, [25]), or slightly alpha1D-vs.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility “in vitro”

Colciago

Mornati

Ferri

et al. 2016

Pharmacological Research

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Prostatic α1‐adrenoceptors: New concepts of function, regulation, and intracellular signaling

Hennenberg

Stief

Gratzke

2013

Neurourology and Urodynamics

205

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Prostatic α1 -adrenoceptors are known to be involved in the pathophysiology of lower urinary tract symptoms (LUTS) in patients with benign prostate obstruction (BPO). It is widely accepted that enhanced α1 -adrenergic smooth muscle contraction can contribute to bladder outlet obstruction; α1 -adrenoceptor antagonists still represent a gold standard in the treatment of LUTS. Accordingly, expression and function of α1 -adrenoceptors in the prostate have attracted large attention over the last three decades. However, recent preclinical studies have challenged our understanding of prostatic α1 -adrenoceptors. In the current review article, we summarize "modern" concepts of prostatic α1 -adrenoceptors which include novel intracellular mediators of contraction as well as non-contractile signaling and post-translational receptor regulation. Configuration of α1 -adrenoceptors with binding partners may determine its function, leading to a dynamic receptor with high functional plasticity. Cooperative regulation of different intracellular effectors (MAPK, Akt, transcription factors) by α1 -adrenoceptors, hormones or growth factors has been suggested. The prostatic α1 -adrenoceptor is no longer being regarded as an isolated, static receptor exclusively mediating prostatic smooth muscle contraction by G proteins, but a dynamic receptor interacting with other receptors within a complex network of mediators.

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Systemic Dysregulation in the Development of Hepatocellular Carcinoma

Zhang

et al. 2012

Primary Liver Cancer

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Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis

Cited by 30 publications

References 37 publications

A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility “in vitro”

A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility “in vitro”

Prostatic α1‐adrenoceptors: New concepts of function, regulation, and intracellular signaling

Systemic Dysregulation in the Development of Hepatocellular Carcinoma

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