Nature-derived compounds modulating Wnt/ -catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases

Sferrazza, Gianluca; Corti, Marco; Brusotti, Gloria; Pierimarchi, Pasquale; Temporini, Caterina; Serafino, Annalucia; Calleri, Enrica

doi:10.1016/j.apsb.2019.12.019

Cited by 55 publications

(42 citation statements)

References 251 publications

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“…Diverse compounds of natural origin or synthetic, peptides and antibodies that are in preclinical studies are shown in Table 2. Natural compounds targeting WNT-signaling have been discussed extensively [174,175], and therefore only few of them are included in Table 2. Several agents influencing WNT-signaling have reached the clinical trials ( Table 3).…”

Section: Wnt-targeted Therapiesmentioning

confidence: 99%

WNT Signaling in Melanoma

Gajos-Michniewicz

Czyż

2020

IJMS

145

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WNT-signaling controls important cellular processes throughout embryonic development and adult life, so any deregulation of this signaling can result in a wide range of pathologies, including cancer. WNT-signaling is classified into two categories: β-catenin-dependent signaling (canonical pathway) and β-catenin-independent signaling (non-canonical pathway), the latter can be further divided into WNT/planar cell polarity (PCP) and calcium pathways. WNT ligands are considered as unique directional growth factors that contribute to both cell proliferation and polarity. Origin of cancer can be diverse and therefore tissue-specific differences can be found in WNT-signaling between cancers, including specific mutations contributing to cancer development. This review focuses on the role of the WNT-signaling pathway in melanoma. The current view on the role of WNT-signaling in cancer immunity as well as a short summary of WNT pathway-related drugs under investigation are also provided.

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Section: Wnt-targeted Therapiesmentioning

confidence: 99%

WNT Signaling in Melanoma

Gajos-Michniewicz

Czyż

2020

IJMS

145

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“…plant varieties. Over the past few decades, natural compounds of plant-based origin have been extensively studied as an exciting class of pharmacologically active molecules [ [22] , [23] , [24] ]. In particular, many natural products have demonstrated potent activity against CoVs [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

Zheng

Disoma

et al. 2021

International Journal of Biological Macromolecules

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SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.

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“…Bacteria and their metabolites can modulate different signalling pathways, including the Wnt/ß-catenin. This pathway has a crucial role in maintenance of adult tissue homeostasis by regulating cell proliferation, migration, differentiation, survival and adhesion, and renewal of stem cells ( Fulbright et al, 2017 ; Sferrazza et al, 2020 ). Bacteroides fragilis enterotoxin promotes cleavage of E-cadherin, an intercellular adhesion molecule that plays a major role in maintaining intestinal epithelial homeostasis in basal and inflammatory conditions ( Rhee et al, 2009 ; Fulbright et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised Medicine

et al. 2021

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Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signalling, hormonal and detoxification pathways. Gut colonisation occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered faecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of oestrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumour tissue and advanced-stage BC when compared with healthy tissue and early stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favours breast tumour carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward a more personalised medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC.

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Nature-derived compounds modulating Wnt/ -catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases

Cited by 55 publications

References 251 publications

WNT Signaling in Melanoma

WNT Signaling in Melanoma

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised Medicine

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