Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer

Muñoz-Moreno, Laura; Arenas, María Isabel; Carmena, Marı́a J.; Sánchez‐Chapado, Manuel; Prieto, Juan Carlos; Bajo, Ana M.

doi:10.18632/oncotarget.10710

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…The exposure of RWPE‐1 cells to GHRH results in tumorigenic transformation since these cells acquire characteristics in common with human PCa cells including hyperproliferative activity, increased gelatinolytic activity of MMP‐2, decreased cell adhesion and increased cell migration. In this regard, GHRH receptor antagonists have been reported to block the effects of GHRH 15,27,28 . All this together corroborates the important role of GHRH as a mediator in the initiation and progression of PCa.…”

Section: Discussionsupporting

confidence: 70%

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

et al. 2022

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Background: Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In this study, we analyzed the carcinogenetic potential of exposure to GHRH of a nontumor human prostate epithelial cell line (RWPE-1) as well as its transforming effect in a xenograft model. Methods: We performed cell viability, cell proliferation, adhesion and migration assays. In addition, metalloprotease (MMP)−2 activity by means gelatin zymography, GHRH-R subcellular location using confocal immunofluorescence microscopy and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunoassay were assessed. Besides, we developed an in vivo model in order vivo model to determine the role of GHRH on tumorigenic transformation of RWPE-1 cells. Results: In cell cultures, we observed development of a migratory phenotype consistent with the gelatinolytic activity of MMP-2, expression of VEGF, as well as E-cadherin-mediated cell-cell adhesion and increased cell motility. Treatment with 0.1 µM GHRH for 24 h significantly increased cell viability and cell proliferation. Similar effects of GHRH were seen in RWPE-1 tumors developed by subcutaneous injection of GHRH-treated cells in athymic nude mice, 49 days after inoculation.Conclusions: Thus, GHRH appears to act as a cytokine in the transformation of RWPE-1 cells by mechanisms that likely involve epithelial-mesenchymal transition, thus reinforcing the role of GHRH in tumorigenesis of prostate.

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Section: Discussionsupporting

confidence: 70%

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

et al. 2022

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“…It is generally accepted that the cell viability correlates well with proliferating potential, and that the conventional approach is the MTT test [31]. The MTT test measures cell viability due to the metabolic activity, by a reduction of the water-soluble, yellow tetrazole salt (MTT) into the insoluble dark blue formazan.…”

Section: Discussionmentioning

confidence: 99%

Bimodular Antiparallel G-Quadruplex Nanoconstruct with Antiproliferative Activity

et al. 2019

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Oligonucleotides with an antiproliferative activity for human cancer cells have attracted attention over the past decades; many of them have a G-quadruplex structure (GQ), and a cryptic target. In particular, DNA oligonucleotide HD1, a minimal GQ, could inhibit proliferation of some cancer cell lines. The HD1 is a 15-nucleotide DNA oligonucleotide that folds into a minimal chair-like monomolecular antiparallel GQ structure. In this study, for eight human cancer cell lines, we have analyzed the antiproliferative activities of minimal bimodular DNA oligonucleotide, biHD1, which has two HD1 modules covalently linked via single T-nucleotide residue. Oligonucleotide biHD1 exhibits a dose-dependent antiproliferative activity for lung cancer cell line RL-67 and cell line of central nervous system cancer U87 by MTT-test and Ki-67 immunoassay. The study of derivatives of biHD1 for the RL-67 and U87 cell lines revealed a structure-activity correlation of GQ folding and antiproliferative activity. Therefore, a covalent joining of two putative GQ modules within biHD1 molecule provides the antiproliferative activity of initial HD1, opening a possibility to design further GQ multimodular nanoconstructs with antiproliferative activity—either as themselves or as carriers.

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“…Studies have shown that GHRH can activate the mitogen-activated protein kinase signaling pathway in MDA-MB-231 human breast cancer cells [ 9 ]. Munoz-Moreno et al [ 10 ] showed that the GHRH antagonist inhibits the growth of the tumor by inhibiting the protein kinase B (Akt) and extracellular signal-regulated kinases (ERKs) signaling pathway in prostate cancer cells. Their study also showed that the GHRH receptor is expressed in cardiac myocytes.…”

Section: Discussionmentioning

confidence: 99%

Effect of growth hormone releasing hormone on chondrocytes of osteoarthritis

2022

Korean J Intern Med

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Background/Aims: To evaluate the effect and possible mechanism of growth hormone releasing hormone (GHRH) on chondrocytes of osteoarthritis (OA). Methods: Articular chondrocytes were cultured and the expression of GHRH receptor in chondrocytes was detected. Then recombinant adenovirus GHRH (Ad-GHRH) was transfected to one group of chondrocytes. The expression of collagen type II, matrix metalloproteinase 13 (MMP-13) and signal transducer and activator of transcription 3 (STAT3) in each experimental group was determined by Western blot. Results: The GHRH receptor was expressed in chondrocytes, and this provided a basis for further study of the role of GHRH in chondrocytes. Cell proliferation of the Ad-GHRH group was significantly higher than that of the OA group by CCK-8 assay. Compared with the OA-group, the protein expression of MMP-13 was decreased in the Ad-GHRH group. Compared with the OA-group, the protein expression of collagen type II, phosphorylated STAT3 (P-STAT3) were increased in the Ad-GHRH group. Conclusions: Our results show that the GHRH receptor is expressed in chondrocytes. GHRH can promote the proliferation of chondrocytes and the synthesis of type II collagen, and increase the extracellular matrix, which is achieved by phosphorylated STAT3 protein.

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Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer

Cited by 8 publications

References 39 publications

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

Bimodular Antiparallel G-Quadruplex Nanoconstruct with Antiproliferative Activity

Effect of growth hormone releasing hormone on chondrocytes of osteoarthritis

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