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Recent Advances in Nuclear Factor Kappa-B (NF-kB) Inhibitors for Cancer...
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Recent Advances in Nuclear Factor Kappa-B (NF-kB) Inhibitors for Cancer Therapy

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 May 2024) | Viewed by 8604

Special Issue Editor

Dr. Hui-Yen Chuang

E-Mail Website
Guest Editor
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
Interests: biomolecular imaging; biology; molecular diagnostics; tumor metabolism; tumor immune microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nuclear Factor kappa-B is a critical transcription factor regulating numerous target genes, such as COX-2, VEGF-C, ICAM-1, survivin, etc. The dysregulation of NF-kB has been linked to developing neurological diseases, immune diseases, and cancer. 

The upregulation of NF-kB and related pathways promotes the development and progression of cancer from different angles, including enhancing angiogenesis and altering metabolic and immune status within the tumor microenvironment. Additionally, NF-kB can be activated by chemotherapy and radiotherapy, contributing to treatment failure and resistance. Therefore, different synthetic and natural compounds targeting NF-kB have been discovered and shown to be effective in cancer treatment. 

Here, in this Special Issue entitled "Recent Advances in Nuclear Factor kappa-B inhibitors for Cancer Therapy", we aim to cover reviews and original research articles describing the development and use of NF-kB inhibitors in cancer treatments alone or in combination with other cancer treatment modalities (e.g., chemotherapy, radiotherapy, and immunotherapy) from different perspectives. We also encourage the discussion of the NF-kB-mediated regulation of signaling pathways involving cancer progression in an original review. This could be a starting point for developing new NF-kB inhibitors and related strategies for cancer treatment.

Dr. Hui-Yen Chuang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NF-kB inhibitors
  • natural compounds
  • metabolism reprogramming
  • immunomodulation
  • combination treatments
  • treatment resistance

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Published Papers (4 papers)

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Research

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21 pages, 5327 KiB  
Article
Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/luc Colon Carcinoma Cells and Tumor-Bearing Animal Model
by Shan-Chih Lee, Chao-Yu Shen, Wei-Hsun Wang, Yen-Po Lee, Keng-Wei Liang, Ying-Hsiang Chou, Yeu-Sheng Tyan and Jeng-Jong Hwang
Pharmaceuticals 2023, 16(9), 1188; https://doi.org/10.3390/ph16091188 - 22 Aug 2023
Cited by 2 | Viewed by 1582
Abstract
Background: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. Methods: CT26/luc murine colon carcinoma cells and a CT26/luc tumor-bearing animal model were [...] Read more.
Background: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. Methods: CT26/luc murine colon carcinoma cells and a CT26/luc tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. Results: Rh2 caused cell cycle arrest at the G1 phase in CT26/luc cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice’s sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. Conclusions: The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer. Full article
(This article belongs to the Special Issue Recent Advances in Nuclear Factor Kappa-B (NF-kB) Inhibitors for Cancer Therapy)
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18 pages, 3982 KiB  
Article
Ganetespib with Methotrexate Acts Synergistically to Impede NF-κB/p65 Signaling in Human Lung Cancer A549 Cells
by Gehad Subaiea, Syed Mohd Danish Rizvi, Hemant Kumar Singh Yadav, Turki Al Hagbani, Marwa Helmy Abdallah, El-Sayed Khafagy, Hosahalli Veerabhadrappa Gangadharappa, Talib Hussain and Amr Selim Abu Lila
Pharmaceuticals 2023, 16(2), 230; https://doi.org/10.3390/ph16020230 - 2 Feb 2023
Cited by 11 | Viewed by 1965
Abstract
Among the various types of cancer, lung cancer accounts for the highest number of fatalities across the globe. A combination of different cancer chemotherapeutics is regarded as an effective strategy for clinical management of different cancers. Ganetespib (GAN) is a well-established hsp90 inhibitor [...] Read more.
Among the various types of cancer, lung cancer accounts for the highest number of fatalities across the globe. A combination of different cancer chemotherapeutics is regarded as an effective strategy for clinical management of different cancers. Ganetespib (GAN) is a well-established hsp90 inhibitor with enhanced pharmacological properties in comparison with its first-generation counterparts. Previous preclinical studies have shown that GAN exerts significant effects against cancer cells; however, its therapeutic effects against non-small cell lung cancer (NSCLC) A549 cells, achieved by modulating the expression of the NF-κB/p65 signaling pathway, remains unexplored. In this study, the combinatorial effect of GAN and methotrexate (MTX) against lung carcinomas was investigated through both in silico and in vitro studies. A combinatorial treatment regimen of GAN/MTX exerted more significant cytotoxic effects (p < 0.001) against A549 cells than individual treatments. The GAN/MTX combination also instigated nuclear fragmentation followed by augmentation in intracellular ROS levels (p < 0.001). The elevated ROS in A549 cells upon exposure to GAN/MTX combinatorial regimen was concomitantly accompanied with a remarkable reduction in mitochondrial viability. In addition, it was observed that the GAN/MTX combination succeeded in elevating caspase-3 activity and downregulating the expression levels of anti-apoptotic mediators Bcl2 and survivin in NSCLC A549 cells. Most importantly, the GAN/MTX combinatorial regimen impeded the activation of the NF-kB/p65 signaling pathway via repression of the expression of E-cadherin and N-cadherin, which was confirmed by molecular docking studies. Collectively, these findings demonstrated the synergistic effect of the GAN/MTX combinatorial regimen in suppressing the growth of A549 cells by modulating the NF-κB/p65 signaling pathway. Full article
(This article belongs to the Special Issue Recent Advances in Nuclear Factor Kappa-B (NF-kB) Inhibitors for Cancer Therapy)
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Review

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33 pages, 4785 KiB  
Review
Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity
by Mariana Medeiros, Sophia Guenka, David Bastos, Karla Laissa Oliveira and María Sol Brassesco
Pharmaceuticals 2024, 17(6), 734; https://doi.org/10.3390/ph17060734 - 5 Jun 2024
Cited by 1 | Viewed by 1331
Abstract
Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the “omics” era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, [...] Read more.
Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the “omics” era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity. Full article
(This article belongs to the Special Issue Recent Advances in Nuclear Factor Kappa-B (NF-kB) Inhibitors for Cancer Therapy)
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22 pages, 8152 KiB  
Review
NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances
by Xuesong Wu, Liang Sun and Fangying Xu
Pharmaceuticals 2023, 16(6), 783; https://doi.org/10.3390/ph16060783 - 24 May 2023
Cited by 9 | Viewed by 2930
Abstract
The transcription factor nuclear factor-κB (NF-κB) plays a complicated role in multiple tumors. Mounting evidence demonstrates that NF-κB activation supports tumorigenesis and development by enhancing cell proliferation, invasion, and metastasis, preventing cell death, facilitating angiogenesis, regulating tumor immune microenvironment and metabolism, and inducing [...] Read more.
The transcription factor nuclear factor-κB (NF-κB) plays a complicated role in multiple tumors. Mounting evidence demonstrates that NF-κB activation supports tumorigenesis and development by enhancing cell proliferation, invasion, and metastasis, preventing cell death, facilitating angiogenesis, regulating tumor immune microenvironment and metabolism, and inducing therapeutic resistance. Notably, NF-κB functions as a double-edged sword exerting positive or negative influences on cancers. In this review, we summarize and discuss recent research on the regulation of NF-κB in cancer cell deaths, therapy resistance, and NF-κB-based nano delivery systems. Full article
(This article belongs to the Special Issue Recent Advances in Nuclear Factor Kappa-B (NF-kB) Inhibitors for Cancer Therapy)
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