VIP induces NF-κB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells

Fernández‐Martínez, Ana B.; Carmena, Marı́a J.; Bajo, Ana M.; Vacas, Eva; Sánchez‐Chapado, Manuel; Prieto, Juan Carlos

doi:10.1016/j.cellsig.2014.11.005

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…The combination with anti-inflammatory and other adjuvant therapies present a very promising treatment approach for this malignancy. Curcumin is a promising anticancer agent for various cancer types including prostate cancer cells, and involves in multiple signaling and potential targets [ 6 , 7 , 19 ]. However, the detailed molecular mechanisms underlining suppression of androgen-independent prostate cancer cell growth still remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

Xiang

Zhang

et al. 2015

J Exp Clin Cancer Res

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BackgroundProstate cancer is one of the most common malignancies in men. The mucin 1 (MUC1) heterodimeric oncoprotein is overexpressed in human prostate cancers with aggressive pathologic and clinical features, resulting in a poor outcome. However, the functional role for MUC1 C-terminal domain (MUC1-C) in androgen-independent prostate cancer occurrence and development has remained unclear.MethodsCell viability was measured by MTT assays. Western blot analysis was performed to measure the phosphorylation and protein expression of SAPK/JNK and ERK1/2, and MUC1-C, NF-κB subunit p65 and p50. Exogenous expression of MUC1-C, NF-κB subunit p65 was carried out by transient and electroporated transfection assays.ResultsWe showed that curcumin inhibited the growth of androgen-independent prostate cancer cells and a synergy was observed in the presence of curcumin and bicalutamide, the androgen receptor antagonist. To further explore the potential mechanism underlining this, we found that curcumin increased the phosphorylation of ERK1/2 and SAPK/JNK, which was enhanced by bicalutamide. In addition, curcumin reduced the protein expression of MUC1-C and NF-κB subunit p65, which were abrogated in the presence of the inhibitors of MEK/ERK1/2 (PD98059) and SAPK/JNK (SP60015). A further reduction was observed in the combination of curcumin with bicalutamide. Moreover, while exogenous expression of MUC1-C had little effect on curcumin-reduced p65, the overexpression of p65 reversed the effect of curcumin on MUC1-C protein expression suggesting that p65 is upstream of MUC1-C. Intriguingly, we showed that exogenous expression of MUC1-C feedback diminished the effect of curcumin on phosphorylation of ERK1/2 and SAPK/JNK, and antagonized the effect of curcumin on cell growth.ConclusionOur results show that curcumin inhibits the growth of androgen-independent prostate cancer cells through ERK1/2- and SAPK/JNK-mediated inhibition of p65, followed by reducing expression of MUC1-C protein. More importantly, there are synergistic effects of curcumin and bicalutamide. The negative feedback regulatory loop of MUC1-C to ERK1/2 and SAPK/JNK further demonstrates the role of MUC1-C that contributes to the overall responses of curcumin. This study unveils the potential molecular mechanism by which combination of curcumin with bicalutamide enhances the growth inhibition of androgen-independent prostate cancer cells.

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Section: Discussionmentioning

confidence: 99%

Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

Xiang

Zhang

et al. 2015

J Exp Clin Cancer Res

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“…The effects of EPAC1 on cancer cell proliferation and survival are shown to be cell-type and context dependent. While EPAC1 inhibits cell proliferation in clear renal cell carcinoma (cRCC) A498 cells (1054), EPAC1 activity stimulates cell proliferation and survival by upregulating Ras/ MAPK and PI3K/Akt/mTOR signaling in prostate cancer cells (295,303,712). Likewise, EPAC1 expression is shown to be increased in human ovarian cancer cells where silencing EPAC1 by small interfering RNA inhibits proliferation and induces cell cycle arrest in vitro, as well as suppresses tumor growth in vivo in xenograft nude mouse models.…”

Section: B Role Of Epac In Cancersmentioning

confidence: 99%

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

Robichaux

Cheng

2018

Physiological Reviews

153

226

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This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively "young" in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses. This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are also discussed.

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“…Addition of VIP to prostrate cancer-cells stimulate cAMP generation; increases the transactivation of HER2/Neu, as well as the transactivation of the androgen receptor via a PKA-ERK mechanism and increases the expression of c-Fos, VEGF and COX-2, the latter dependent on activation of EPAC, NF-kB, PI3K and ERK[116•, 117-121]. VIP has a carcinogenic potential as it induces the malignant transformation of the human prostate non-tumor epithelial cell-RWPE-1, with stimulation of MMP2, MMP9, cyclin D1; decreased E-cadherin-mediated-cell-cell adhesion, increased cell motility and cell proliferation[122].…”

Section: Vip/pacap: Prostate-cancermentioning

confidence: 99%

Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer

Moody¹,

Nuche-Berenguer

Jensen

2016

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review To summarize the roles of VIP/PACAP and their receptors(VPAC1, VPAC2/PAC1) in human tumors as well as their role in potential novel treatments. Recent findings Considerable progress has been made in understanding of the effects of VIP/PACAP on growth of various tumors as well as in the signaling cascades involved, especially of the role of transactivation of the Epidermal growth factor(EGF) family. The overexpression of VPAC1/2, PAC1 on a number of common neoplasms (breast, lung, prostate, CNS, neuroblastoma) is receiving increased attention both as a means of tumor imaging the location and extent of these tumors, as well as for targeted directed treatment, by coupling cytotoxic agents to VIP/PACAP analogues. Summary VIP/PACAP has prominent growth effects on a number of common neoplasms, which frequently overexpressed the three subtypes of their receptors. The increased understanding of their signaling cascades, effect on tumor growth/differentiation, and the use of the overexpression of these receptors for localization/targeted cytotoxic delivery, are all suggesting possible novel tumor treatments.

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VIP induces NF-κB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells

Cited by 14 publications

References 32 publications

Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer

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