Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells

Yemelyanov, Alexander; Czwornog, Jennifer; Gera, Lajos; Joshi, Sonali; Chatterton, Robert T.; Budunova, Irina

doi:10.1158/0008-5472.can-07-6104

Cited by 53 publications

(89 citation statements)

References 47 publications

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“…This is in accordance with the observed inhibition of p65 translocation by CpdA and DEX in the lung. Similarly, CpdA also prevented translocation of the p65 subunit of NF-kB in prostate cells, whereas in the same cells, classic GCs induced transrepression without affecting nuclear translocation of NF-kB (38). Another report demonstrates that CpdA, but not DEX, can inhibit NF-kB nuclear translocation in primary murine microglia but not in astrocytes (8).…”

Section: Discussionmentioning

confidence: 96%

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Reber

Daubeuf

Plantinga

et al. 2012

The Journal of Immunology

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The glucocorticoid receptor (GR) is a transcription factor able to support either target gene activation via direct binding to DNA or gene repression via interfering with the activity of various proinflammatory transcription factors. An improved therapeutic profile for combating chronic inflammatory diseases has been reported through selectively modulating the GR by only triggering its transrepression function. We have studied in this paper the activity of Compound A (CpdA), a dissociated GR modulator favoring GR monomer formation, in a predominantly Th2-driven asthma model. CpdA acted similarly to the glucocorticoid dexamethasone (DEX) in counteracting OVA-induced airway hyperresponsiveness, recruitment of eosinophils, dendritic cells, neutrophils, B and T cells, and macrophages in bronchoalveolar lavage fluid, lung Th2, Tc2, Th17, Tc17, and mast cell infiltration, collagen deposition, and goblet cell metaplasia. Both CpdA and DEX inhibited Th2 cytokine production in bronchoalveolar lavage as well as nuclear translocation of NF-κB and its subsequent recruitment onto the IκBα promoter in the lung. By contrast, DEX but not CpdA induces expression of the GR-dependent model gene MAPK phosphatase 1 in the lung, confirming the dissociative action of CpdA. Mechanistically, we demonstrate that CpdA inhibited IL-4–induced STAT6 translocation and that GR is essential for CpdA to mediate chemokine repression. In conclusion, we clearly show in this study the anti-inflammatory effect of CpdA in a Th2-driven asthma model in the absence of transactivation, suggesting a potential therapeutic benefit of this strategy.

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Section: Discussionmentioning

confidence: 96%

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Reber

Daubeuf

Plantinga

et al. 2012

The Journal of Immunology

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“…In this respect, the detection of phospho-Elk-1, a protein acting as a transcription factor activating specific genes, might be considered as a suitable and very sensitive marker of acute radiation-induced injury of large and small intestine [8] . Whether Elk-1 inhibitors, such as the compound A (CpdA) or the protective agent U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)-butadiene], the effect of which probably results from the IL-1β mRNA reduction via the inhibition of ERK pathway, can be used in the management of this syndrome remains to be investigated [9,10] . Inflammator y cell infiltration of the colon is observed at an early stage of radiation-induced colitis.…”

Section: Empirical-experimental Managementmentioning

confidence: 99%

Recent advances in the management of radiation colitis

Kountouras¹,

Zavos²

2008

WJG

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“…It has been suggested that dexamethasone has certain anti-angiogenic and anti-tumor effects (5,6). In addition, dexamethasone may also inhibit proliferation and induce differentiation in numerous tissue-derived carcinoma cells, such as gynecological and digestive system tumor cells (7)(8)(9). However, little research has been performed on the inhibitory effect of dexamethasone on lung carcinoma cells, particularly for patients who received palliative surgery.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of dexamethasone on residual Lewis lung cancer cells in mice following palliative surgery

Sun

Wang

et al. 2016

Oncology Letters

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Abstract. Previous studies found that glucocorticoids were closely associated with the oncogenesis and development of numerous types of tumors. The aim of the present study was to investigate the effect of dexamethasone on the growth and angiogenesis of Lewis lung cancer cells in mice who received palliative surgery. Lewis lung carcinoma cells were inoculated subcutaneously into the right axilla of C57BL/6 mice. When tumor diameter reached 0.5 cm, 2 weeks later, palliative surgery was performed, and the mice were randomly divided into 3 groups with 6 animals in each group (control group, cisplatin group and dexamethasone group). From the first postoperative day, all the mice were administered with saline, cisplatin or dexamethasone for 10 days, and changes in xenograft tumor volumes were monitored. Cisplatin and dexamethasone were dissolved in normal saline (0.9%). All mice were sacrificed on postoperative day 11, and the whole body and the local tumors were weighed immediately. The expression levels of hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen and the microvessel density (MVD) in the tumor mass, were measured by immunohistochemistry, western blotting and quantitative polymerase chain reaction. In the present study, tumor growth was inhibited in the cisplatin group and dexamethasone group, and the weights of tumors were significantly decreased in the cisplatin group and dexamethasone group compared with the control group (P<0.001). The expression levels of HIF-1α and VEGF and the MVD were significantly lower in the cisplatin group and dexamethasone group than in the control group (P<0.01). In conclusion, dexamethasone can inhibit the growth and angiogenesis of residual Lewis lung carcinoma subsequent to palliative surgery partially through downregulation of HIF-1α and VEGF signaling pathways.

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Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells

Abstract: Androgen receptor (AR)-and glucocorticoid receptor (GR

Cited by 53 publications

References 47 publications

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Recent advances in the management of radiation colitis

Inhibitory effect of dexamethasone on residual Lewis lung cancer cells in mice following palliative surgery

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