Expression and role of the angiotensin II AT2 receptor in human prostate tissue: In search of a new therapeutic option for prostate cancer

Guimond, Marie Odile; Battista, M.-C.; Nikjouitavabi, Fatemeh; Carmel, Maude; Barrès, Véronique; Doueik, Alexandre A.; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo‐Payet, Nicole

doi:10.1002/pros.22653

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…Contrary to AGTR1, AGTR2 was not detected in 58 ovarian cancer tissues, which suggests the down-regulation of AGTR2 in ovarian cancers. Although there is no report in ovarian cancers, AGTR2 was evaluated in prostate cancers [24,25]. In those studies, increased expression of AGTR2 induced cell apoptosis and selective AGTR2 stimulation decreased nontumoral prostate cell number.…”

Section: Discussionmentioning

confidence: 99%

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Park

Choi

et al. 2014

Gynecologic Oncology

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Section: Discussionmentioning

confidence: 99%

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Park

Choi

et al. 2014

Gynecologic Oncology

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“…First-strand synthesis (5 μg total RNA) was carried out with SuperScript II Reverse Transcriptase using Oligo-dT [12][13][14][15][16][17][18] oligonucleotides (Invitrogen Life Technologies). The RNA quantity and quality were determined by a spectrophotometer.…”

Section: Isolation Of Rna and Rt-pcrmentioning

confidence: 99%

“…We, therefore, studied the expression of AT 2 receptors in human uterine leiomyosarcoma cells and control human uterine smooth muscle cells (HutSMC), including their presence in mitochondria, and assessed their roles in the induction of apoptosis and cell death. C21 has been tested in a broad variety of cardiovascular and neurological models, such as myocardial infarction, hypertension-induced vascular remodelling, stroke, spinal cord injury and Alzheimer's disease, however, besides one study [14], the AT 2 receptor agonist has not yet been used in cancer research. A few peptide AT 2 receptor agonists have been designed based on the modification of the Ang II molecule.…”

Section: Introductionmentioning

confidence: 99%

Activation of intracellular angiotensin AT2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

et al. 2015

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The presence of angiotensin type 2 (AT₂) receptors in mitochondria and their role in NO generation and cell aging were recently demonstrated in various human and mouse non-tumour cells. We investigated the intracellular distribution of AT₂ receptors including their presence in mitochondria and their role in the induction of apoptosis and cell death in cultured human uterine leiomyosarcoma (SK-UT-1) cells and control human uterine smooth muscle cells (HutSMC). The intracellular levels of the AT₂ receptor are low in proliferating SK-UT-1 cells but the receptor is substantially up-regulated in quiescent SK-UT-1 cells with high densities in mitochondria. Activation of the cell membrane AT₂ receptors by a concomitant treatment with angiotensin II and the AT₁ receptor antagonist, losartan, induces apoptosis but does not affect the rate of cell death. We demonstrate for the first time that the high-affinity, non-peptide AT₂ receptor agonist, Compound 21 (C21), penetrates the cell membrane of quiescent SK-UT-1 cells, activates intracellular AT₂ receptors and induces rapid cell death; approximately 70% of cells died within 24 h. The cells, which escaped cell death, displayed activation of the mitochondrial apoptotic pathway, i.e. down-regulation of the Bcl-2 protein, induction of the Bax protein and activation of caspase-3. All quiescent SK-UT-1 cells died within 5 days after treatment with a single dose of C21. C21 was devoid of cytotoxic effects in proliferating SK-UT-1 cells and in quiescent HutSMC. Our results point to a new, unique approach enabling the elimination non-cycling uterine leiomyosarcoma cells providing that they over-express the AT₂ receptor.

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“…AT 1 Blood vessels [1], brain [2], kidney [3,4], * gingiva [5], eye [6], heart [7], placenta [8], uterus [9] and pancreas [10] AT 2 Blood vessels [1,11], brain [2], kidney [3,4], prostate [12], * gingiva [5], heart [7,13], uterus [9] and pancreas [10] AT 4 Blood vessels [14], brain [15] and heart [16] Mas Brain [17], kidney [3], uterus [18], ovary [19] and testis [20] B 1 Brain [21][22][23], * bone [24], * urinary bladder [25], * spinal cord [26], kidney [27,28] and trachea [29] B 2 * Brain [30], * liver [31], * bone [24], * adrenal gland [32], heart [33], * pancreas [34], trachea [29] and * kidney [3...…”

Section: Receptor Tissue Distributionmentioning

confidence: 99%

“…Interestingly, the induction of VEGF expression in the rat retina by AngII seems to be modulated by both AT 1 and AT 2 receptors [174]. The inhibitory effect of AngII acting via the AT 2 receptor on cells isolated from prostate tissues suggests that the activation of this receptor may inhibit cell proliferation [176]. The AT 2 receptor is expressed not only in the tumour microenvironment blood vessels, but may also be present in some cancer cells.…”

Section: Angiotensins In Cancermentioning

confidence: 99%

Non-canonical signalling and roles of the vasoactive peptides angiotensins and kinins

et al. 2014

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GPCRs (G-protein-coupled receptors) are among the most important targets for drug discovery due to their ubiquitous expression and participation in cellular events under both healthy and disease conditions. These receptors can be activated by a plethora of ligands, such as ions, odorants, small ligands and peptides, including angiotensins and kinins, which are vasoactive peptides that are classically involved in the pathophysiology of cardiovascular events. These peptides and their corresponding GPCRs have been reported to play roles in other systems and under pathophysiological conditions, such as cancer, central nervous system disorders, metabolic dysfunction and bone resorption. More recently, new mechanisms have been described for the functional regulation of GPCRs, including the transactivation of other signal transduction receptors and the activation of G-protein-independent pathways. The existence of such alternative mechanisms for signal transduction and the discovery of agonists that can preferentially trigger one signalling pathway over other pathways (called biased agonists) have opened new perspectives for the discovery and development of drugs with a higher specificity of action and, therefore, fewer side effects. The present review summarizes the current knowledge on the non-canonical signalling and roles of angiotensins and kinins.

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Expression and role of the angiotensin II AT2 receptor in human prostate tissue: In search of a new therapeutic option for prostate cancer

Cited by 23 publications

References 48 publications

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Activation of intracellular angiotensin AT2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

Non-canonical signalling and roles of the vasoactive peptides angiotensins and kinins

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