NF-κB Signaling Pathway Inhibitors as Anticancer Drug Candidates

Barbosa, Maria Letícia de Castro; Conceição, Raissa Alves da; Fraga, Aline Guerra Manssour; Camarinha, Barbara Dias; Silva, Gabriela Cristina de Carvalho; Lima, Antonio Gilclêr Ferreira; Cardoso, Elisama Azevedo; Lione, Viviane de Oliveira Freitas

doi:10.2174/1871520616666160729112854

Cited by 53 publications

(35 citation statements)

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“…Moreover, triggering of NF‐κB pathway has already been considered as one of the most significant mechanisms in acquired resistance to chemotherapy and radiotherapy (X. Chen, Kandasamy, & Srivastava, ). These results demonstrate that the inhibition of NF‐κB signaling cascade could be a promising approach to overcome cancer cells resistance to the therapeutic agents (de Castro Barbosa et al, ). Baicalein from Scutellaria baicalensis has been identified as an inhibitor of NF‐κB activation, which suppressed TNF‐α‐induced NF‐κB activation in a dose‐dependent manner.…”

Section: Flavonoids Functional Mechanisms In Leukemia Cellsmentioning

confidence: 71%

Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

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Section: Flavonoids Functional Mechanisms In Leukemia Cellsmentioning

confidence: 71%

Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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“…Interestingly, similar with LY29400, transfection with IkBa vectors could prominently increase the apoptosis proportion induced by CXCR4 shRNA, whereas treatment with IKKa vectors could significantly decrease the cell apoptosis induced by down-regulation of CXCR4 in osteosarcoma cells. The roles of PI3K-AKT and NF-κβ in the regulation of cell growth, proliferation and apoptosis had been extensively investigated [39, 40]. Previous studies revealed that PI3K/AKT/NF-κβ signaling pathway played a vital role in regulating apoptosis in various cancer cells [41-44].…”

Section: Discussionmentioning

confidence: 99%

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. Methods: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κβ signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κβ promoter luciferase reporter plasmid. The expression and activation of NF-κβ Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κβ signaling after the down-regulation of CXCR4 in osteosarcoma cells. Results: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κβ signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. Conclusions: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κβ signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

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“…A number of studies found that NF-κB signaling pathway plays highly important roles in cell proliferation, apoptosis, angiogenesis, in ammation, metastasis, and drug resistance. [23][24][25] A variety of stimuli coalesce on NF-κB activation, which can in turn mediate varied transcriptional programs. 26 In this study, the protein expression of P65, IκBα, and their phosphorylated were detected by western blot.…”

Section: Discussionmentioning

confidence: 99%

MiR-381 enhances the sensitivity of non-small cell lung cancer to radiotherapy by targeting ROCK2 to regulate NF-κB signaling pathway

Huang

Zeng

Zhang

et al. 2020

Preprint

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BackgroundWe investigated the effect of miR-381 on the sensitivity of non-small cell lung cancer (NSCLC) to radiotherapy, and examined its possible mechanism.MethodsNSCLC A549 cells and miR-381 overexpression and gene silencing cell lines were treated with radiotherapy. The cell proliferation was tested by CCK-8 assay and colony formation. Flow cytometry and TUNEL were used to detect the cell apoptosis. The expression of nuclear factor kappa B (NF-κB) signaling pathway related proteins were detected by western blot. NF-κB signaling pathway activator and inhibitor cell lines were further constructed and the above experiments were repeated. Double luciferase assay was used to verify the target of miR-381. Furthermore, a nude mouse xenograft model was constructed and treated with radiotherapy. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was observed by immunohistochemistry. The apoptosis related proteins in tumor tissues were detected by western blot.ResultsThe mRNA expression of miR-381 was increased after radiotherapy treatment. Radiotherapy treatment also can inhibit the proliferation and promote apoptosis of A549 cells. Compared with radiotherapy group, cell proliferation was significantly decreased and apoptosis was significantly increased in miR-381 overexpression group (p < 0.05). Moreover, ROCK2 is a target of miR-381, and overexpression of miR-381 can down-regulate the expression of ROCK2 protein. In nude mice, miR-381 mimic interference can reduce cell tumorigenicity and proliferation, and increase the apoptosis. However, the indicators above were contrary in miR-381 silencing group. Verification experiments further verify that NF-κB signaling pathway activator can reverse the role of miR-381.ConclusionMiR-381 overexpression could enhance the sensitivity of NSCLC to radiotherapy by targeting ROCK2 to inhibit NF-κB signaling pathway.

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NF-κB Signaling Pathway Inhibitors as Anticancer Drug Candidates

Cited by 53 publications

References 0 publications

Leukemia therapy by flavonoids: Future and involved mechanisms

Leukemia therapy by flavonoids: Future and involved mechanisms

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

MiR-381 enhances the sensitivity of non-small cell lung cancer to radiotherapy by targeting ROCK2 to regulate NF-κB signaling pathway

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