NF-κB-Dependent and -Independent (Moonlighting) IκBα Functions in Differentiation and Cancer

Espinosa, Lluís; Marruecos, Laura

doi:10.3390/biomedicines9091278

Cited by 4 publications

(5 citation statements)

References 86 publications

(112 reference statements)

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“…These data were compared with the results of the FSK treatment. FSK is an adenylate cyclase activator that acts by increasing the Besides, IκBα is a crucial regulator of the transcription factor NF-κB, and deregulation of IκBα cellular levels impacts a variety of diseases, including chronic inflammatory diseases and cancers (34,35). Western blotting results revealed that ketoprofen-RGD increased IκBα protein expression and counteracted the suppressive effects of LPS.…”

Section: Discussionmentioning

confidence: 99%

Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells

2023

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Background: Naringenin (Nar) has anti-inflammatory and anticarcinogenic properties. Arginine-glycine- aspartate (RGD) is a tripeptidic sequence used as an integrin ligand and targeting system for delivering chemotherapeutic agents to cancer cells. Objectives: In this study, the inhibitory effects of Nar and ketoprofen-RGD on leukemia and ovarian cancer cells (K562 and SKOV3) were explored for the first time, focusing on their proliferation activity and their anti-inflammatory capacity. Methods: Analyses were conducted on the calmodulin (CaM)-dependent phosphodiesterase 1 (PDE1) activation by ketoprofen-RGD, Nar, and their combination. These drugs’ effects on protein kinase A (PKA) activation, intracellular cyclic adenosine monophosphate (cAMP) level, and PDE1 inhibition were identified. Later, it was also evaluated if ketoprofen-RGD alone or in combination with Nar had anti-inflammatory effects. Results: Nar improved the antagonizing consequences of ketoprofen-RGD on the CaM protein, which hinders PDE1, improving PKA activity and cAMP levels. A mixture of ketoprofen-RGD and Nar and ketoprofen-RGD alone diminished K562 and SKOV3 cell viability through the cAMP/PKA pathway by inhibiting PDE1 and CaM. These two compounds showed anti-inflammatory effects on both cell lines. Conclusions: This study indicated for the first time that combining ketoprofen-RGD and Nar can be a promising anti-inflammatory therapeutic regimen for treating leukemia and ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells

2023

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“…The NFKB inhibitor alpha ( NFKBIA ) gene at 14q13.2 encodes the alpha subunit of the inhibitors of κB (IκBα), proteins that regulate the activity of transcription factor nuclear factor κB (NF-κB) in the cytoplasm. 23 Evidence that, in chromatin, nuclear NFKBIA dynamically interacts with histones H2A and H4 to regulate polycomb-dependent transcriptional repression and, thus, stem cell maturation, lineage specification, and cancer 24 , 25 , 26 and our characterization of NFKBIA as a tumor suppressor in glioblastoma 27 prompted our investigation of the relationship of NFKBIA deletions with other genetic markers, alterations in the methylome, and the clinical course of gliomas. We analyzed the genetic profiles of gliomas of multiple well-characterized patient populations to determine whether incorporation of NFKBIA deletions could enhance the prognostic value of current molecular descriptions.…”

Section: Introductionmentioning

confidence: 99%

Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas

Bredel,

Espinosa,

Kim

et al. 2023

Cell Reports Medicine

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“…Then, N‐terminal part of p100 that shows NF‐κB2 p52 translocates into the nucleus by binding to RelB (Cildir et al, 2016; Feige et al, 2018). More details about NF‐κB signaling can be found in recent reviews (Figure 1) (Espinosa & Marruecos, 2021; Gilmore, 2021; Silke & O'Reilly, 2021).…”

Section: Introductionmentioning

confidence: 99%

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Mirzaei

Saghari

Bassiri

et al. 2022

Journal Cellular Physiology

101

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Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial‐to‐mesenchymal transition (EMT) is a well‐known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor‐kappaB (NF‐κB) is one of them. The nuclear translocation of NF‐κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF‐κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF‐κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor‐β, and Slug as inducers of EMT undergo upregulation by NF‐κB to promote metastasis of tumor cells. After EMT induction driven by NF‐κB, a significant decrease occurs in E‐cadherin levels, while N‐cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF‐κB/EMT axis in cancers. Moreover, NF‐κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF‐κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.

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NF-κB-Dependent and -Independent (Moonlighting) IκBα Functions in Differentiation and Cancer

Cited by 4 publications

References 86 publications

Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells

Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells

Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

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