The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo

Hackler, László; Ózsvári, Béla; Gyuris, Márió; Sipos, Péter; Fábián, Gabriella; Molnár, Eszter; Marton, Annamária; Faragó, Nóra; Mihály, József; Nagy, L; Szénási, Tibor; Diron, Andrea; Párducz, Á.; Kanizsai, Iván; Puskás, László G.

doi:10.1371/journal.pone.0149832

Cited by 49 publications

(34 citation statements)

References 53 publications

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“…The curcumin analog C150 significantly and markedly reduces neuronal cell death and DNA mutation in brain tissue by suppressing NF‐κβ (Hackler et al . ). Similarly, increased levels of omega‐3 polyunsaturated fatty acid (eicosapentaenoic acid) in the brain of mice also reduces the inflammatory response to LPS challenge via NF‐κβ pathways.…”

Section: Therapeutic Potential Of Biological Compounds Against Nf‐κβ–mentioning

confidence: 97%

Nuclear factor‐kappa β as a therapeutic target for Alzheimer's disease

Jha¹,

Jha

Kar

et al. 2019

Journal of Neurochemistry

113

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Alzheimer's disease (AD) is a typical progressive, chronic neurodegenerative disorder with worldwide prevalence. Its clinical manifestation involves the presence of extracellular plaques and intracellular neurofibrillary tangles (NFTs). NFTs occur in brain tissues as a result of both Ab agglomeration and Tau phosphorylation. Although there is no known cure for AD, research into possible cures and treatment options continues using cell-cultures and model animals/organisms. The nuclear factor-kappa b (NF-jb) plays an active role in the progression of AD. Impairment to this signaling module triggers undesirable phenotypic changes such as neuroinflammation, activation of microglia, oxidative stress related complications, and apoptotic cell death. These imbalances further lead to homeostatic abnormalities in the brain or in initial stages of AD essentially pushing normal neurons toward the degeneration process. Interestingly, the role of NF-jb signaling associated receptor-interacting protein kinase is currently observed in apoptotic and necrotic cell death, and has been reported in brains. Conversely, the NF-jb signaling pathway has also been reported to be involved in normal brain functioning. This pathway plays a crucial role in maintaining synaptic plasticity and balancing between learning and memory. Since any impairment in the pathways associated with NF-jb signaling causes altered neuronal dynamics, neurotherapeutics using compounds including, antioxidants, bioflavonoids, and non-steroidal anti-inflammatory drugs against such abnormalities offer possibilities to rectify aberrant excitatory neuronal activity in AD. In this review, we have provided an extensive overview of the crucial role of NF-jb signaling in normal brain homeostasis. We have also thoroughly outlined several established pathomechanisms associated with NF-jb pathways in AD, along with their respective therapeutic approaches.

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Section: Therapeutic Potential Of Biological Compounds Against Nf‐κβ–mentioning

confidence: 97%

Nuclear factor‐kappa β as a therapeutic target for Alzheimer's disease

Jha¹,

Jha

Kar

et al. 2019

Journal of Neurochemistry

113

View full text Add to dashboard Cite

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“…Legumain targeted nanoparticles encapsulating hydrazinocurcumin suppressed STAT3 and re-educated TAMs, to be IL-12 high , IL-10 low and TGF-β low , which resulted in suppression of tumor growth, metastasis and angiogenesis in vivo [160]. Several new curcumin derivatives have been synthesized and were confirmed to have anticancer activities, however their potential effects on TAMs and MDSCs would be interesting to test [161]. Another inhibitor of JAK1 and STAT3, a synthetic triterpenoid, bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid, also known as CDDO-Me) abrogated the immune suppressive effect of MDSCs on CD8+ cytotoxic T-cells resulting in decreased tumor growth in mice [162,163].…”

Section: Therapeutic Interventions Targeting Tams and Mdscs Tuninmentioning

confidence: 99%

Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets

Szebeni¹,

Vízler

Nagy³

et al. 2016

IJMS

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Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review some of these indisputable experimental and clinical evidences of cancer related smouldering inflammation. The most common myeloid infiltrate in solid tumors is composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). These cells promote tumor growth by several mechanisms, including their inherent immunosuppressive activity, promotion of neoangiogenesis, mediation of epithelial-mesenchymal transition and alteration of cellular metabolism. The pro-tumoral functions of TAMs and MDSCs are further enhanced by their cross-talk offering a myriad of potential anti-cancer therapeutic targets. We highlight these main pro-tumoral mechanisms of myeloid cells and give a general overview of their phenotypical and functional diversity, offering examples of possible therapeutic targets. Pharmacological targeting of inflammatory cells and molecular mediators may result in therapies improving patient condition and prognosis. Here, we review experimental and clinical findings on cancer-related inflammation with a major focus on creating an inventory of current small molecule-based therapeutic interventions targeting cancer-related inflammatory cells: TAMs and MDSCs.

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“…A time-dependent decrease in cell area and an increase in maximum thickness was seen [31]. DH microscopy was also used to analyze the effect of the cell death-inducing curcumin analog C-150 [32]. Four different glioblastoma cell lines were treated with 1 μM of the analog for 24 h. The results showed significantly increased cell volume and average thickness and decreased cell area for the cell lines investigated.…”

Section: Cell Death Of Adherent Cellsmentioning

confidence: 99%

Holography: The Usefulness of Digital Holographic Microscopy for Clinical Diagnostics

El-Schich¹,

Kamlund²,

Janicke³

et al. 2017

Holographic Materials and Optical Systems

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Digital holographic (DH) microscopy is a digital high-resolution holographic imaging technique with the capacity of quantification of cellular conditions without any staining or labeling of cells. The unique measurable parameters are the cell number, cell area, thickness, and volume, which can be coupled to proliferation, migration, cell cycle analysis, viability, and cell death. The technique is cell friendly, fast and simple to use and has unique imaging capabilities for time-lapse investigations on both the single cell and the cell-population levels. The interest for analyzing specifically cell volume changes with DH microscopy, resulting from cytotoxic treatments, drug response, or apoptosis events has recently increased in popularity. We and others have used DH microscopy showing that the technique has the sensitivity to distinguish between different cells and treatments. Recently, DH microscopy has been used for cellular diagnosis in the clinic, providing support for using the concept of DH, e.g., screening of malaria infection of red blood cells (RBC), cervix cancer screening, and sperm quality. Because of its quick and label-free sample handling, DH microscopy will be an important tool in the future for personalized medicine investigations, determining the optimal therapeutic concentration for both different cancer types and individual treatments.

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The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo

Cited by 49 publications

References 53 publications

Nuclear factor‐kappa β as a therapeutic target for Alzheimer's disease

Nuclear factor‐kappa β as a therapeutic target for Alzheimer's disease

Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets

Holography: The Usefulness of Digital Holographic Microscopy for Clinical Diagnostics

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