Naringenin-Mediated ATF3 Expression Contributes to Apoptosis in Human Colon Cancer

Song, Hun Min; Park, Gwang Hun; Jeong, Jin Boo

doi:10.4062/biomolther.2015.109

Cited by 51 publications

(28 citation statements)

References 38 publications

(46 reference statements)

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“…In a recent study, p38 was demonstrated to be activated by naringenin and to mediate the upregulation of ATF3 in human colon cancer cells32. However, our results showed that naringenin inhibited p38 activation in LPS-treated macrophages, suggesting that p38 may not be required for ATF3 upregulation in macrophages.…”

Section: Discussioncontrasting

confidence: 80%

The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway

Liu

Wang

Fan

et al. 2016

Sci Rep

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Excessive activation of the TLR4 signalling pathway is critical for inflammation-associated disorders, while negative regulators play key roles in restraining TLR4 from over-activation. Naringenin is a citrus flavonoid with remarkable anti-inflammatory activity, but the mechanisms underlying its inhibition of LPS/TLR4 signalling are less clear. This study investigated the molecular targets and therapeutic effects of naringenin in vitro and in vivo. In LPS-stimulated murine macrophages, naringenin suppressed the expression of TNF-α, IL-6, TLR4, inducible NO synthase (iNOS), cyclo-oxygenase-2 (COX2) and NADPH oxidase-2 (NOX2). Naringenin also inhibited NF-κB and mitogen-activated protein kinase (MAPK) activation. However, it did not affect the IRF3 signalling pathway or interferon production, which upregulate activating transcription factor 3 (ATF3), an inducible negative regulator of TLR4 signalling. Naringenin was demonstrated to directly increase ATF3 expression. Inhibition of AMPK and its upstream calcium-dependent signalling reduced ATF3 expression and dampened the anti-inflammatory activity of naringenin. In murine endotoxaemia models, naringenin ameliorated pro-inflammatory reactions and improved survival. Furthermore, it induced AMPK activation in lung tissues, which was required for ATF3 upregulation and the enhanced anti-inflammatory activity. Overall, this study reveals a novel mechanism of naringenin through AMPK-ATF3-dependent negative regulation of the LPS/TLR4 signalling pathway, which thereby confers protection against murine endotoxaemia.

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Section: Discussioncontrasting

confidence: 80%

The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway

Liu

Wang

Fan

et al. 2016

Sci Rep

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“…ATF3 promotion of apoptosis, a key process in prevention of growth and invasion, may result from KLF6 induction of ATF3 [144] or through its activation of p53 [145]. We found a significant downregulation of KLF6 in the centre KE (p = 0.02) and interestingly, ATF3 has been shown to mediate apoptosis by anti-cancer therapies [146–148]. Also in the microdissected KE, UGT3A2 , a member of the UDP-glycosyltransferase superfamily that plays a role in drug metabolism and which may affect detoxification of therapeutic drugs, was found to be strongly under-expressed [149, 150].…”

Section: Resultsmentioning

confidence: 86%

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

et al. 2017

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Keloid disease (KD) is a fibroproliferative cutaneous tumour characterised by heterogeneity, excess collagen deposition and aggressive local invasion. Lack of a validated animal model and resistance to a multitude of current therapies has resulted in unsatisfactory clinical outcomes of KD management. In order to address KD from a new perspective, we applied for the first time a site-specific in situ microdissection and gene expression profiling approach, through combined laser capture microdissection and transcriptomic array. The aim here was to analyse the utility of this approach compared with established methods of investigation, including whole tissue biopsy and monolayer cell culture techniques. This study was designed to approach KD from a hypothesis-free and compartment-specific angle, using state-of-the-art microdissection and gene expression profiling technology. We sought to characterise expression differences between specific keloid lesional sites and elucidate potential contributions of significantly dysregulated genes to mechanisms underlying keloid pathobiology, thus informing future explorative research into KD. Here, we highlight the advantages of our in situ microdissection strategy in generating expression data with improved sensitivity and accuracy over traditional methods. This methodological approach supports an active role for the epidermis in the pathogenesis of KD through identification of genes and upstream regulators implicated in epithelial-mesenchymal transition, inflammation and immune modulation. We describe dermal expression patterns crucial to collagen deposition that are associated with TGFβ-mediated signalling, which have not previously been examined in KD. Additionally, this study supports the previously proposed presence of a cancer-like stem cell population in KD and explores the possible contribution of gene dysregulation to the resistance of KD to conventional therapy. Through this innovative in situ microdissection gene profiling approach, we provide better-defined gene signatures of distinct KD regions, thereby addressing KD heterogeneity, facilitating differential diagnosis with other cutaneous fibroses via transcriptional fingerprinting, and highlighting key areas for future KD research.

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“…prostate, pancreatic, colon, breast, and gastric cancer (Song et al, 2016;Lim et al, 2017;Wang et al, 2019a) sensitizing chemotherapy CDKN2A, BCL2, CASP3/9, BAX, PTK2, MAPK14 lung and pancreatic cancer (Parashar et al, 2018;Lee et al, 2019) inhibiting metabolism AKT1, GTF2H2, MAP2K1/2, MAPK1, NFKB1, PIK3CA breast cancer (Harmon and Patel, 2004) enhancing immunity GZMB, ID2, IFNG, IRF2, SMAD3/7 lung cancer and melanoma (Lian et al, 2018) Naringin anti-proliferation AKT1, BIRC5, CDKN1A, CTNNB1, EGFR, MAPK1, MIR126, MTOR, NFKB, PIK3CA, VCAM1…”

Section: Discussionmentioning

confidence: 99%

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

Cao

Han

et al. 2020

Front. Pharmacol.

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Considerable pharmacological studies have demonstrated that the extracts and ingredients from different parts (seeds, peels, pulps, and flowers) of Litchi exhibited anticancer effects by affecting the proliferation, apoptosis, autophagy, metastasis, chemotherapy and radiotherapy sensitivity, stemness, metabolism, angiogenesis, and immunity via multiple targeting. However, there is no systematical analysis on the interaction network of "multiple ingredients-multiple targets-multiple pathways" anticancer effects of Litchi. In this study, we summarized the confirmed anticancer ingredients and molecular targets of Litchi based on published articles and applied network pharmacology approach to explore the complex mechanisms underlying these effects from a perspective of system biology. The top ingredients, top targets, and top pathways of each anticancer function were identified using network pharmacology approach. Further intersecting analyses showed that Epigallocatechin gallate (EGCG), Gallic acid, Kaempferol, Luteolin, and Betulinic acid were the top ingredients which might be the key ingredients exerting anticancer function of Litchi, while BAX, BCL2, CASP3, and AKT1 were the top targets which might be the main targets underling the anticancer mechanisms of these top ingredients. These results provided references for further understanding and exploration of Litchi as therapeutics in cancer as well as the application of "Component Formula" based on Litchi's effective ingredients.

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Naringenin-Mediated ATF3 Expression Contributes to Apoptosis in Human Colon Cancer

Cited by 51 publications

References 38 publications

The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway

The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

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