Curcumin arrests G-quadruplex in the nuclear hyper-sensitive III<sub>1</sub> element of <i>c-MYC</i> oncogene leading to apoptosis in metastatic breast cancer cells

Roy, Ananya; Chatterjee, Oishika; Banerjee, Nilanjan; Roychowdhury, Tanaya; Dhar, Gopa; Mukherjee, Gopeswar; Chatterjee, Subhrangsu

doi:10.1080/07391102.2021.1940284

Cited by 12 publications

(5 citation statements)

References 64 publications

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“…The polyphenol, curcumin, is the main active ingredient in turmeric, a spice widely recognized for its medicinal properties including anti-inflammatory and anti-oxidative activities [517,518]. Curcumin can reduce MYC expression, followed by histone 19 (H19) induction, leading to regulation of specific pro-proliferative TFs in the pro-metastasis microenvironment [519][520][521][522]. Furthermore, curcumin can reverse these processes by increasing levels of tumor suppressors, such as p53, and inducing apoptosis in an EZH2-miR-101 reciprocal negative feedback loop [519,523,524].…”

Section: Curcuminmentioning

confidence: 99%

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

Chan,

Zhang,

et al. 2024

Aging and disease

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Various diseases, including cancers, age-associated disorders, and acute liver failure, have been linked to the oncogene, MYC . Animal testing and clinical trials have shown that sustained tumor volume reduction can be achieved when MYC is inactivated, and different combinations of therapeutic agents including MYC inhibitors are currently being developed. In this review, we first provide a summary of the multiple biological functions of the MYC oncoprotein in cancer treatment, highlighting that the equilibrium points of the MYC/MAX, MIZ1/MYC/MAX, and MAD (MNT)/MAX complexes have further potential in cancer treatment that could be used to restrain MYC oncogene expression and its functions in tumorigenesis. We also discuss the multifunctional capacity of MYC in various cellular cancer processes, including its influences on immune response, metabolism, cell cycle, apoptosis, autophagy, pyroptosis, metastasis, angiogenesis, multidrug resistance, and intestinal flora. Moreover, we summarize the MYC therapy patent landscape and emphasize the potential of MYC as a druggable target, using herbal medicine modulators. Finally, we describe pending challenges and future perspectives in biomedical research, involving the development of therapeutic approaches to modulate MYC or its targeted genes. Patients with cancers driven by MYC signaling may benefit from therapies targeting these pathways, which could delay cancerous growth and recover antitumor immune responses.

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Section: Curcuminmentioning

confidence: 99%

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

Chan,

Zhang,

et al. 2024

Aging and disease

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“…This study demonstrates that curcumin can stabilise and maintain the parallel configuration of the indigenous c-MYC-quadruplex sequences. Curcumin interacts to the 3′ termini of the c-MYC quadruplex to develop a stable complex, according to the findings of molecular docking and MD modelling experiments [ 69 ]. Curcumin's binding affinities and specificity to c-MYC G-quadruplex confirms curcumin as a viable natural product to be exploited as a drug-model to build G-quadruplex targeted ligands.…”

Section: Interaction Of G-quadruplex Dnas With Dietary Flavonoidsmentioning

confidence: 99%

Structural insights and shedding light on preferential interactions of dietary flavonoids with G-quadruplex DNA structures: A new horizon

Bag¹,

Burman²,

Bhowmik³

2023

Heliyon

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“…Moreover, the HDOCK software [45,46] was exploited for the molecular docking studies described in this work. HDOCK is a docking software employed in macromoleculemacromolecule [45] and macromolecule-small molecule [47] docking simulations, including those involving RNA and DNA G-quadruplex structures [48,49]. This server uses ITScore-PP, an iterative knowledge-based scoring function, ranking the Top 1-10 poses provided after the docking runs.…”

Section: Molecular Modelling and In Silico Pharmacokinetic Properties...mentioning

confidence: 99%

Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems

et al. 2023

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The design, synthesis and characterization of a novel nucleoamino acid derivative based on an l-tryptophanamide functionalised with a thymine nucleobase (named TrpT) is here described. The novel construct’s tendency to self-assemble into supramolecular networks in aqueous solution was demonstrated by dynamic light scattering (DLS), circular dichroism (CD), fluorescence and UV spectroscopic measurements. TrpT nanoaggregates showed good stability (up to 5 h) at 140 µM and proved to comprise species of mean hydrodynamic diameter 330 nm and a homogeneous size distribution; scanning electron microscopy (SEM) analysis further revealed these to be spherical-shaped assemblies. The ability of TrpT nanoaggregates to bind curcumin, selected as a model anticancer drug, was also evaluated and its release was monitored over time by confocal microscopy. Molecular docking studies were performed on both TrpT self-assembly and curcumin-loaded nanoaggregates suggesting that the phytomolecule can be accommodated in the interior of the supramolecular network via hydrophobic (π−π and π-alkyl) interactions; the formation of TrpT-curcumin adducts may improve the polarity of the highly-hydrophobic curcumin with a resulting logP closer to the optimal values expected for a good drug bioavailability, as estimated by the ADMETlab software. Finally, the high stability of TrpT nanoassembly in human serum, and the absence of significant toxic effects on human model cells in a cell viability assay, were also demonstrated. Despite its thymine-based scaffold, TrpT was shown not to bind adenine-bearing nucleic acids, suggesting that this interaction is hindered by its intrinsic propensity to self-assemble in preference to forming A-T base pairings. Instead, TrpT was able to interact with a serum protein such as bovine serum albumin (BSA), known to improve the bloodstream transportation and bioavailability of its cargo. Collectively, our findings support the potential use of TrpT for the development of new drug delivery systems. Graphical abstract

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Curcumin arrests G-quadruplex in the nuclear hyper-sensitive III₁ element of c-MYC oncogene leading to apoptosis in metastatic breast cancer cells

Cited by 12 publications

References 64 publications

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

Structural insights and shedding light on preferential interactions of dietary flavonoids with G-quadruplex DNA structures: A new horizon

Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems

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Curcumin arrests G-quadruplex in the nuclear hyper-sensitive III1 element of c-MYC oncogene leading to apoptosis in metastatic breast cancer cells

Cited by 12 publications

References 64 publications

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

Structural insights and shedding light on preferential interactions of dietary flavonoids with G-quadruplex DNA structures: A new horizon

Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems

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Product

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Curcumin arrests G-quadruplex in the nuclear hyper-sensitive III₁ element of c-MYC oncogene leading to apoptosis in metastatic breast cancer cells