Computational analysis of nuclear factor-κB and resveratrol in colorectal cancer

Dariya, Begum; Behera, Santosh Kumar; Srivani, Gowru; Farran, Batoul; Alam, Afroz; Nagaraju, Ganji Purnachandra

doi:10.1080/07391102.2020.1757511

Cited by 11 publications

(5 citation statements)

References 38 publications

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“… 29 , 40 Hydrophobic interactions can occur between nonpolar or hydrophobic regions of molecules, with such interactions possibly contributing to stabilizing protein-ligand complexes. 41 Resveratrol, being a polyphenolic compound with a hydrophobic core, 42 is likely to engage in hydrophobic interactions with hydrophobic patches on NQO1 or other nearby residues. These interactions can facilitate the binding of resveratrol to NQO1 and influence its biological effects.…”

Section: Discussionmentioning

confidence: 99%

In Silico Analysis Determining the Binding Interactions of NAD(P)H: Quinone Oxidoreductase 1 and Resveratrol via Docking and Molecular Dynamic Simulations

Behera,

Lambring,

Hashmi

et al. 2023

ejb

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Objective: NAD(P)H: Quinone oxidoreductase1 (NQO1) plays a crucial role in cellular defense against oxidative stress. Overexpression of NQO1 is linked to various cancer pathways. Despite its potential, the actual mechanisms to inhibit NQO1 and increase the efficacy of standard therapeutic options are not yet established. Resveratrol is an anti-cancer polyphenol found in dietary products and red wine. The objective of this investigation is to employ in silico methods to explore how resveratrol interacts with NQO1. Materials and Methods: Docking analysis of resveratrol against NQO1 was performed using Glide. The most efficiently docked complex was characterized and analyzed by measuring intermolecular (IM) hydrogen (H)-bonds and binding energy values, additional hydrophobic, and electrostatic interactions. IM interaction between complexed protein and compound was demonstrated using LigPlot+ and the Schrödinger ligand interaction module. Molecular dynamics tools were employed to examine the physical movement of molecules to evaluate how macromolecular structures relate to their functions. Results: The results of this investigation depicted a strong affinity of resveratrol against NQO1 followed by MD simulations (NQO1-resveratrol complex-binding energy: −2.847kcal/mol). Resveratrol’s robust binding affinity through docking and molecular dynamic simulations highlights a significant change around 90 ns. The H-bonds number was inversely linked with the resveratrol-NQO1 complex stability. The NQO1-Resveratrol complex displayed dynamic motion, as revealed by porcupine projections, indicating alterations in its movement and flexibility. Conclusion: The present in silico analysis suggests a possible alteration in resveratrol’s orientation in the protein binding pocket. The findings encourage further investigation, including validation using in vitro and in vivo assays.

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Section: Discussionmentioning

confidence: 99%

In Silico Analysis Determining the Binding Interactions of NAD(P)H: Quinone Oxidoreductase 1 and Resveratrol via Docking and Molecular Dynamic Simulations

Behera,

Lambring,

Hashmi

et al. 2023

ejb

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show abstract

“…Much evidence suggests that resveratrol is a multi-factorial bioactive phytochemical with numerous beneficial preventive effects on subcellular biological pathways, especially anti-inflammatory effects by inhibiting pro-inflammatory cytokines (IL-1β, TNF-α, and TNF-β), the pro-inflammatory transcription factor NF-κB and thus NF-κB-promoted end-proteins. A recent molecular docking study documented that resveratrol could be effective against CRC by targeting NF-κB signaling [ 206 ], and in this regard, our group described resveratrol’s NF-κB suppression by resveratrol associated with an anti-inflammatory mode of action in CRC [ 207 ]. Furthermore, a seven-day treatment with resveratrol (10mg/kg body weight) suppressed the dextran sulfate sodium-induced inflammatory colon injury via down-regulation of NF-κB, STAT3, ERK, and iNOS expressions in IRC mice [ 208 ].…”

Section: Resveratrol’s Versatile Anti-carcinogenic Effectsmentioning

confidence: 99%

Resveratrol as sensitizer in colorectal cancer plasticity

Brockmueller

Sajeev

Koklesová

et al. 2023

Cancer Metastasis Rev

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Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that can be linked to several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition of the sentinel gene p53, and apoptosis. As a consequence, tumor cells can escape the effectiveness of chemotherapeutic agents. This underscores the need for cross-target therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Resveratrol, a natural polyphenolic phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the most effective natural chemopreventive agents. Abundant in vitro and in vivo studies have shown that resveratrol, in interaction with standard drugs, is an effective chemosensitizer for CRC cells to chemotherapeutic agents and thus prevents drug resistance by modulating multiple pathways, including transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to modify multiple subcellular pathways that may suppress cancer cell plasticity and reversal of chemoresistance are critical parameters for understanding its anti-cancer effects. In this review, we focus on the chemosensitizing properties of resveratrol in CRC and, thus, its potential importance as an additive to ongoing treatments. Graphical abstract

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“…In C33A, HeLa, CaLo, and CaSki cell cultures, the antiproliferative and proapoptotic activities of resveratrol were accompanied by a significant decrease in NF-κB p65 expression [ 263 ]. In human colon cancer cell cultures, resveratrol prevented nuclear translocation of NF-κB, presumably by binding to its monomer, and thus preventing its dimerization [ 264 ]. This phenolic compound was also able to suppress proliferation of human MV3 and A375 melanoma cells, both in culture and in a mouse xenograft model, by downregulating the expression of NF-κB and NF-κB-regulated miR-221, thus leading to the enhancement of the expression of TFG tumor suppressors, the mRNA of which is targeted by miR-221 [ 265 ].…”

Section: Tumor-promoting Inflammationmentioning

confidence: 99%

Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms

Lyubitelev

Studitsky

2023

IJMS

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Malignant tumors remain one of the main sources of morbidity and mortality around the world. A chemotherapeutic approach to cancer treatment poses a multitude of challenges, primarily due to the low selectivity and genotoxicity of the majority of chemotherapeutic drugs currently used in the clinical practice, often leading to treatment-induced tumors formation. Highly selective antitumor drugs can largely resolve this issue, but their high selectivity leads to significant drawbacks due to the intrinsic tumor heterogeneity. In contrast, plant polyphenols can simultaneously affect many processes that are involved in the acquiring and maintaining of hallmark properties of malignant cells, and their toxic dose is typically much higher than the therapeutic one. In the present work we describe the mechanisms of the action of polyphenols on cancer cells, including their effects on genetic and epigenetic instability, tumor-promoting inflammation, and altered microbiota.

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Computational analysis of nuclear factor-κB and resveratrol in colorectal cancer

Cited by 11 publications

References 38 publications

In Silico Analysis Determining the Binding Interactions of NAD(P)H: Quinone Oxidoreductase 1 and Resveratrol via Docking and Molecular Dynamic Simulations

In Silico Analysis Determining the Binding Interactions of NAD(P)H: Quinone Oxidoreductase 1 and Resveratrol via Docking and Molecular Dynamic Simulations

Resveratrol as sensitizer in colorectal cancer plasticity

Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms

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