scholarly journals Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

2012 ◽  
Vol 214 (3) ◽  
pp. 389-398 ◽  
Author(s):  
B Shan ◽  
C Schaaf ◽  
A Schmidt ◽  
K Lucia ◽  
M Buchfelder ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cell Cultures ◽  
Curcuma Longa ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Gh3 Cells ◽  
Mrna Synthesis ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Adenoma Cell

Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plantCurcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. Here we have studied in rodent and human pituitary tumour cells the influence of curcumin on the production of hypoxia inducible factor 1α (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat pituitary tumour cells as well as in all human pituitary adenoma cell cultures (n=32) studied. Under hypoxia-mimicking conditions (CoCl2treatment) in AtT20 and GH3 cells as well as in all human pituitary adenoma cell cultures (n=8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human pituitary adenoma cell cultures investigated (n=18). Thus, curcumin may inhibit pituitary adenoma progression not only through previously demonstrated anti-proliferative and pro-apoptotic actions but also by its suppressive effects on pituitary tumour neovascularisation.

A human pituitary adenoma cell line proliferates and maintains some differentiated functions following expression of SV40 large T-antigen

1998 ◽  
Vol 9 (2) ◽  
pp. 169-184 ◽  
Author(s):  
Long Jin ◽  
Elzbieta Kulig ◽  
Xiang Qian ◽  
Bernd W. Scheithauer ◽  
Norman L. Eberhardt ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cell Line ◽  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Adenoma Cell

Specific Somatostatin Receptors on Human Pituitary Adenoma Cell Membranes*

1985 ◽  
Vol 61 (4) ◽  
pp. 666-671 ◽  
Author(s):  
SHOICHIRO IKUYAMA ◽  
HAJIME NAWATA ◽  
KEN'ICHI KATO ◽  
TSUYOSHI KARASHIMA ◽  
HIROSHI IBAYASHI ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cell Membranes ◽  
Somatostatin Receptors ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Adenoma Cell

scholarly journals Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

2005 ◽  
Vol 152 (2) ◽  
pp. 293-300 ◽  
Author(s):  
S A Borg ◽  
K E Kerry ◽  
J A Royds ◽  
R D Battersby ◽  
T H Jones
Keyword(s):  
Pituitary Adenoma ◽  
Tumour Volume ◽  
Pituitary Tumour ◽  
Angiogenic Factor ◽  
Tumour Cell Line ◽  
Pituitary Tumours ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Invasive Status ◽  
Significant Addition

Objectives: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion. Methods: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1α and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging. Results: VEGF was detected in conditioned medium of HP75 cells (900±52 pg/ml) and in 82% of tumours tested (range 26–16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P = 0.056; VEGF, P < 0.001 (P values based on Spearman’s test)) and IL1α produced (volume, P < 0.005; VEGF, P < 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1α, but not IL6, significantly increased VEGF production. Conclusions: The significant associations between VEGF and the levels of IL6 and IL1α suggest an important role for these cytokines in the development of these tumours.

scholarly journals RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells

2011 ◽  
Vol 19 (1) ◽  
pp. 13-27 ◽  
Author(s):  
B Shan ◽  
J Gerez ◽  
M Haedo ◽  
M Fuertes ◽  
M Theodoropoulou ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Hypoxia Inducible Factor ◽  
Pituitary Tumour ◽  
Mrna Levels ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Adaptive Processes ◽  
Endothelial Growth Factor

The recently cloned small RWD-domain containing protein RSUME was shown to increase protein levels of hypoxia-inducible factor-1α (HIF-1α). The latter is the oxygen-regulated subunit of HIF-1, the most important transcription factor of the cellular adaptive processes to hypoxic conditions. It is also a major regulator of vascular endothelial growth factor-A (VEGF-A), which is critically involved in the complex process of tumour neovascularisation. In this study, the expression and role of RSUME in pituitary tumours was studied. We found that RSUME mRNA was up-regulated in pituitary adenomas and significantly correlated with HIF-1α mRNA levels. Hypoxia (1% O2) or treatment with hypoxia-mimicking CoCl2enhanced RSUME and HIF-1α expression, induced translocation of HIF-1α to the nuclei and stimulated VEGF-A production both in pituitary tumour cell lines and primary human pituitary adenoma cell cultures. When RSUME expression was specifically down-regulated by siRNA, the CoCl2-induced increase VEGF-A secretion was strongly reduced which was shown to be a consequence of the RSUME knockdown-associated reduction of HIF-1α synthesis. Thus, RSUME plays an important role in initiating pituitary tumour neovascularisation through regulating HIF-1α levels and subsequent VEGF-A production and may therefore be critically involved in pituitary adenoma progression.

scholarly journals Somatostatin analogues stimulate p27 expression and inhibit the MAP kinase pathway in pituitary tumours

2006 ◽  
Vol 155 (2) ◽  
pp. 371-379 ◽  
Author(s):  
Erika Hubina ◽  
Alexandra M Nanzer ◽  
Matthew R Hanson ◽  
Enrica Ciccarelli ◽  
Marco Losa ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Map Kinase ◽  
Kinase Inhibitor ◽  
Gh3 Cells ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Protein Levels ◽  
Map Kinase Pathway ◽  
Kinase Pathway

Objectives: Somatostatin (SST) analogues play an important role in the medical management of somatotroph pituitary adenomas and new agonists have the potential to be effective in a wider group of pituitary and other tumours. The anti-proliferative effect of SST occurs through multiple mechanisms, one of which is cell-cycle arrest, where p27, a cyclin-dependent kinase inhibitor, is an important regulator. We hypothesised that SST may upregulate p27 protein levels and downregulate the MAP kinase pathway in these tumours. Methods: Human pituitary adenoma cells and rat pituitary cell line (GH3) were cultured and treated in vitro with octreotide and the broad-spectrum SST agonist SOM230 (pasireotide). Immunoblotting for p27 and phospho-ERK (pERK) was performed and proliferation assessed by [3H]-thymidine incorporation. Histological samples from acromegalic patients treated with octreotide before surgery were immunostained for p27 and compared to samples from untreated patients matched for sex, age, tumour size, extension and invasiveness. Results: We detected upregulation of p27 protein levels with SST analogue treatment in vitro in human pituitary adenoma samples. pERK1/2 was inhibited by SST analogues in both the human samples and GH3 cells. SST and its analogues inhibited the proliferation of GH3 cells. p27 immunostaining was stronger in samples from patients with longer preoperative octreotide treatment (more than 6 months) than in samples from patients with shorter treatment periods. Conclusions: This study demonstrates that SST-mediated growth inhibition is associated with the downregulation of pERK and upregulation of p27. More potent and broader-spectrum SST analogues are likely to play an increasing role in the treatment of tumours, where the MAP kinase pathway is overactivated.

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