Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Lagunas‐Rangel, Francisco Alejandro; Bermúdez‐Cruz, Rosa María

doi:10.3389/fonc.2020.598174

Cited by 23 publications

(19 citation statements)

References 112 publications

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“…Many studies described the significant role of phytochemicals in modulating epigenetic changes and metabolic reprogramming—key events for cancer initiation, promotion, and progression [ 36 , 37 ]. Preclinical trials using breast cancer models demonstrated oncostatic effects of secondary metabolites of plants via modulation of critical enzymes contributing to aerobic glycolysis [ 38 ], detoxification and antioxidant machinery [ 39 ], DNA repair mechanisms [ 40 ], or programmed cell death [ 25 ]. In addition, phytochemicals can in experimental models of breast cancer restore global and gene-specific promoter DNA methylation patterns [ 41 ], alter the gene expression by modulating miRNA expression [ 42 ], or affect histone modifications [ 43 ].…”

Section: Pleiotropic Effects Of Phytochemicals Demonstrated In Vitro ...mentioning

confidence: 99%

Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

et al. 2022

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Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread, supporting immune system and increasing effectiveness of conventional anti-cancer therapies, among others. Molecular and sub-/cellular mechanisms are highly complex affecting several pathways considered potent targets for advanced diagnostics and cost-effective treatments. Demonstrated anti-cancer affects, therefore, are clinically relevant for improving individual outcomes and might be applicable to the primary (protection against initial cancer development), secondary (protection against potential metastatic disease development), and tertiary (towards cascading complications) care. However, a detailed data analysis is essential to adapt treatment algorithms to individuals’ and patients’ needs. Consequently, advanced concepts of patient stratification, predictive diagnostics, targeted prevention, and treatments tailored to the individualized patient profile are instrumental for the cost-effective application of natural anti-cancer substances to improve overall breast cancer management benefiting affected individuals and the society at large.

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Section: Pleiotropic Effects Of Phytochemicals Demonstrated In Vitro ...mentioning

confidence: 99%

Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

et al. 2022

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“…SIRT1 showed a reciprocal regulation with AGTR1, so that at high levels of SIRT1 the expression of AGTR1 decreased (Diaz-Ruiz et al 2015 ). Indeed, resveratrol, a polyphenol activator of SIRT1 and which has been shown to prolong lifespan of several species, inhibits the expression of AGTR1 at the transcriptional level (Valenzano et al 2006 ; Miyazaki et al 2008 ; Lagunas-Rangel and Bermúdez-Cruz 2020 ). Previously, a longer survival of hypertensive rats was observed with long-term treatment using the AGTR1 blockers enalapril, losartan, valsartan and ME3221 (Nagura et al 1995 ; Mercier et al 2007 ).…”

Section: Gpcr Influencing Lifespanmentioning

confidence: 99%

G protein-coupled receptors that influence lifespan of human and animal models

Lagunas‐Rangel

2021

Biogerontology

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Humanity has always sought to live longer and for this, multiple strategies have been tried with varying results. In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while maintaining good health since they have a substantial participation in a wide variety of processes of human pathophysiology and are one of the main therapeutic targets. In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human models, and in which we put a special interest in describing the molecular mechanisms involved. Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling and the AMPK and TOR pathways, and those that alter oxidative homeostasis and severe and/or chronic inflammation. We also discuss the possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan and healthspan.

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“…Several groups have reported that trans ‐resveratrol and its analogues, in addition to producing DNA damage, activate DNA repair mechanisms in various cancer cell lines, including prostate, colon and breast cancer cells [26–28] …”

Section: Introductionmentioning

confidence: 99%

Plant‐Derived Stilbenoids as DNA‐Binding Agents: From Monomers to Dimers

Platella

Mazzini

Napolitano

et al. 2021

Chemistry A European J

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Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (±)‐trans‐δ‐viniferin, deriving from trans‐resveratrol dimerization, was investigated in its ability to target DNA duplex and G‐quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (±)‐trans‐δ‐Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3’‐ and 5’‐ends of a G‐quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (±)‐trans‐δ‐viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (±)‐trans‐δ‐viniferin and trans‐resveratrol, i. e. (±)‐pterostilbene‐trans‐dihydrodimer and trans‐pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at μM concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G‐quadruplex structures.

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Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Cited by 23 publications

References 112 publications

Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

G protein-coupled receptors that influence lifespan of human and animal models

Plant‐Derived Stilbenoids as DNA‐Binding Agents: From Monomers to Dimers

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