Molecular docking analysis of nuclear factor-κB and genistein interaction in the context of breast cancer

Mukund, Vidya; Behera, Santosh Kumar; Alam, Afroz

doi:10.6026/97320630015011

Cited by 24 publications

(19 citation statements)

References 17 publications

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“…In the past, epidemiologic and preclinical evidence has suggested that phytochemicals have several health benefits [124]. Recent studies have demonstrated that phytoestrogen might produce a positive impact on menopausal women, with the benefit of no increased risk of breast and uterine cancer or cardiovascular disease [12,14,22,30,42]. Moreover, evidence from randomized clinical trials has suggested that soy extracts may relieve menopause-related vasomotor symptoms [38,39].…”

Section: Discussionmentioning

confidence: 99%

“…Genistein acts as a chemotherapeutic agent by modifying different types of pathways, such as altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis [14,30,69]. As mentioned above, the main targets are kinesin-like protein 20A (KIF20A), Wnt/β-catenin, PI3K/AKT, ERK1/2, caspases, Bax, Bcl-2, NF-κB, and MAPK, and signaling pathways may act as the molecular mechanisms of the anticancer therapeutic effects of genistein, among others [14,19,30,75,77,78,84,87,88,89,90,91,92]. The synergistic behavior of genistein with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, also suggested that it could play a potential role in synergistic therapy [125].…”

Section: Discussionmentioning

confidence: 99%

“…Abbreviations: 5-HIAA: 5-Hydroxyindoleacetic acid; 5-HT: serotonin; HDL: high-density lipoprotein; LDL: low-density lipoprotein; MAO: monoamine oxidase; TNF-α tumor necrosis factor alpha. Information is supported by references [28,29,30,31,32,33,34]. …”

Section: Figurementioning

confidence: 99%

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Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

et al. 2019

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Plant-derived compounds have recently attracted greater interest in the field of new therapeutic agent development. These compounds have been widely screened for their pharmacological effects. Polyphenols, such as soy-derived isoflavones, also called phytoestrogens, have been extensively studied due to their ability to inhibit carcinogenesis. These compounds are chemically similar to 17β-estradiol, and mimic the binding of estrogens to its receptors, exerting estrogenic effects in target organs. Genistein is an isoflavone derived from soy-rich products and accounts for about 60% of total isoflavones found in soybeans. Genistein has been reported to exhibit several biological effects, such as anti-tumor activity (inhibition of cell proliferation, regulation of the cell cycle, induction of apoptosis), improvement of glucose metabolism, impairment of angiogenesis in both hormone-related and hormone-unrelated cancer cells, reduction of peri-menopausal and postmenopausal hot flashes, and modulation of antioxidant effects. Additionally, epidemiological and clinical studies have reported health benefits of genistein in many chronic diseases, such as cardiovascular disease, diabetes, and osteoporosis, and aid in the amelioration of typical menopausal symptoms, such as anxiety and depression. Although the biological effects are promising, certain limitations, such as low bioavailability, biological estrogenic activity, and effects on target organs, have limited the clinical applications of genistein to some extent. Moreover, studies report that modification of its molecular structure may eliminate the biological estrogenic activity and its effects on target organs. In this review, we summarize the potential benefits of genistein on menopause symptoms and menopause-related diseases like cardiovascular, osteoporosis, obesity, diabetes, anxiety, depression, and breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

et al. 2019

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“…Minimum distance and distance fluctuation matrix of these pro-tein structures were acquired from each MD trajectory on the time interval 20-50 ns. [43] Protein Expression and Purification: Full-length human NQO1, NQO2, or mutation-NQO2 was cloned into the GST fusion vector pGEX-4T-1. The expression plasmids were transfected into Escherichia coli BL21 and the cells grown in LB medium with ampicillin (100 µg mL −1 ) at 37°C, until the optical density at 600 nm (OD600) reached 0.6-0.8.…”

Section: Methodsmentioning

confidence: 99%

Curcumol Overcomes TRAIL Resistance of Non‐Small Cell Lung Cancer by Targeting NRH:Quinone Oxidoreductase 2 (NQO2)

Zhang

Zhou

et al. 2020

Advanced Science

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Resistance to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) of cancer cell remains a key obstacle for clinical cancer therapies. To overcome TRAIL resistance, this study identifies curcumol as a novel safe sensitizer from a food-source compound library, which exhibits synergistic lethal effects in combination with TRAIL on non-small cell lung cancer (NSCLC). SILAC-based cellular thermal shift profiling identifies NRH:quinone oxidoreductase 2 (NQO2) as the key target of curcumol. Mechanistically, curcumol directly targets NQO2 to cause reactive oxygen species (ROS) generation, which triggers endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) death receptor (DR5) signaling, sensitizing NSCLC cell to TRAIL-induced apoptosis. Molecular docking analysis and surface plasmon resonance assay demonstrate that Phe178 in NQO2 is a critical site for curcumol binding. Mutation of Phe178 completely abolishes the function of NQO2 and augments the TRAIL sensitization. This study characterizes the functional role of NQO2 in TRAIL resistance and the sensitizing function of curcumol by directly targeting NQO2, highlighting the potential of using curcumol as an NQO2 inhibitor for clinical treatment of TRAIL-resistant cancers.

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“…Ligands that cause conformational changes in receptors usually show high fluctuations in Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Radius of Gyration (Rg) graphs [79]. When calculating the Free energy contribution of electrostatic energy (ELE), Van der Waals (VDW), total gas-phase energy, nonpolar and polar contributions to solvation (PBSOL and GBSOL) and entropic (T∆S) states were taken into account.…”

Section: Molecular Dynamics Studiesmentioning

confidence: 99%

Mitigate the cytokine storm due to the severe COVID-19: A computational investigation of possible allosteric inhibitory actions on IL-6R and IL-1R using selected phytochemicals

et al. 2020

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The novel corona virus 2019 (COVID 19) is growing at an increasing rate with high mortality. Meanwhile, the cytokine storm is the most dangerous and potentially life-threatening event related to COVID 19. Phyto-compounds found in existing Ayurveda drugs have the ability to inhibit the Interleukin 6 (IL-6R) and Interleukin 1 (IL-1R) receptors. IL-6R and IL-1R receptors involve in cytokine storm and recognition of phytochemicals with proven safety profiles could open a pathway to the development of the most effective drugs against cytokine storm. In this study, we intend to perform an in silico investigation of effective phyto compounds, which can be isolated from selected medicinal herbs to avoid cytokine storm, inhibiting the IL-6 and IL-1 receptor binding process. An extensive literature survey followed by virtual screening was carried out to identify phytochemicals with potential anti-hyper-inflammatory action. Flexible docking was conducted for validated models of IL-1R and IL-6R-α with the most promising phytochemicals at possible allosteric sites using AutoDock Vina. Molecular dynamics (MD) studies were conducted for selected protein-ligand complexes using LARMD server and conformational changes were evaluated. According to the results, taepeenin J had Gibbs energy (ΔG) of -10.85 kcal/mol towards IL-1R but had limited oral bioavailability. MD analysis revealed that taepeenin J can cause significant conformational movements in IL-1R. Nortaepeenin B showed a ΔG of -8.5 kcal/mol towards IL-6R-α with an excellent oral bioavailability. MD analysis predicted that it can cause significant conformational movements in IL-6R-α. Hence, the evaluated phytochemicals are potential candidates for further in vitro studies for the development of medicine against cytokine storm on behalf of SARS-COV-2 infected patients.

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Molecular docking analysis of nuclear factor-κB and genistein interaction in the context of breast cancer

Cited by 24 publications

References 17 publications

Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

Curcumol Overcomes TRAIL Resistance of Non‐Small Cell Lung Cancer by Targeting NRH:Quinone Oxidoreductase 2 (NQO2)

Mitigate the cytokine storm due to the severe COVID-19: A computational investigation of possible allosteric inhibitory actions on IL-6R and IL-1R using selected phytochemicals

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