Dietary Cancer Chemopreventive Agents – Targeting Inflammation and Nrf2 Signaling Pathway

Khor, Tin Oo; Yu, Siwang; Kong, Ah‐Ng Tony

doi:10.1055/s-0028-1088303

Cited by 66 publications

(51 citation statements)

References 86 publications

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“…Protein thiocarbamoylation can be a powerful modulator of protein function and is, for example, considered to play a key role in the induction of phase II carcinogen-metabolising enzymes by ITCs via induction of the Nrf2 transcription factor [18,19]. PEITC appears to bind to proteins more readily than SFN, perhaps accounting for its more potent apoptosis promoting activity [Mi Isothiocyanates and angiogenesis -7 -2007].…”

Section: Chemistry and Metabolism Of Itcsmentioning

confidence: 99%

“…For example, direct covalent modification of the negative regulator kelch-like ECH-associated protein 1 (Keap1) by SFN is thought to contribute to activation of Nrf2, required for activation of phase II carcinogeninactivating enzymes and protection from carcinogen-induced cancer [18,19,48,49]. Interestingly, a number of reactive chemical compounds have been shown to inhibit NF-B activity via direct covalent modification of NF-B signalling pathway components.…”

Section: Hif-independent Control Of Angiogenesismentioning

confidence: 99%

See 1 more Smart Citation

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Cavell

Alwi

Donlevy

et al. 2011

Biochemical Pharmacology

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To cite this version:Breeze E. Cavell, Sharifah S. Syed Alwi, Alison Donlevy, Graham Packham. Anti-angiogenic effects of dietary isothiocyanates; mechanisms of action and implications for human health. Biochemical Pharmacology, Elsevier, 2010, 81 (3) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Isothiocyanates and angiogenesis -3 - AbstractIsothiocyanates (ITCs) are electrophilic compounds derived from plants and are thought to play a major role in the potential chemopreventive effects associated with high intake of cruciferous vegetables. ITCs are also being evaluated for chemotherapeutic activity in early phase clinical trials. In addition to their effects on carcinogen metabolism and cancer cell survival and proliferation, ITCs have been shown to effectively interfere with angiogenesis in vitro and in vivo. Angiogenesis is the development of a new blood supply from existing vasculature and is required for tumours to develop beyond a small size limit determined by the diffusion limit for oxygen. Inhibition of angiogenesis may play a key role in the potential chemopreventive/chemotherapeutic activity of ITCs. In this review we highlight recent data demonstrating that ITCs have anti-angiogenic activity and identify potential molecular targets for these effects, including hypoxia-inducible factor (HIF), nuclear factor B (NF-B), activator protein 1 (AP1) and tubulin. We also discuss these findings in light of the potential chemopreventive/chemotherapeutic effects of ITCs.

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Section: Chemistry and Metabolism Of Itcsmentioning

confidence: 99%

Section: Hif-independent Control Of Angiogenesismentioning

confidence: 99%

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Cavell

Alwi

Donlevy

et al. 2011

Biochemical Pharmacology

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“…We theorized that the nonpolar fractions of licorice and chrysanthemum, may possess anti-inflammatory and anti-oxidative stress properties that could be further developed for diseases prevention including cancer chemoprevention. In this study, we aim to investigate the transcription regulation of LE and CZ on the transcriptional factor nuclear erythroid-related factor 2 (Nrf2) signaling pathway that controls the expression of many antioxidative stress and phase II drug metabolizing (DM)/ detoxifying enzymes, which are typically elicited by many chemopreventive compounds (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory/Anti-oxidative Stress Activities and Differential Regulation of Nrf2-Mediated Genes by Non-Polar Fractions of Tea Chrysanthemum zawadskii and Licorice Glycyrrhiza uralensis

Khor

Saw

et al. 2010

AAPS J

155

127

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Abstract. Accumulating evidence from epidemiological studies indicates that chronic inflammation and oxidative stress play critical roles in neoplastic development. The aim of this study was to investigate the anti-inflammatory, anti-oxidative stress activities, and differential regulation of Nrf2-mediated genes by tea Chrysanthemum zawadskii (CZ) and licorice Glycyrrhiza uralensis (LE) extracts. The antiinflammatory and anti-oxidative stress activities of hexane/ethanol extracts of CZ and LE were investigated using in vitro and in vivo approaches, including quantitative real-time PCR (qPCR) and microarray. Additionally, the role of the transcriptional factor Nrf2 (nuclear erythroid-related factor 2) signaling pathways was examined. Our results show that CZ and LE extracts exhibited potent antiinflammatory activities by suppressing the mRNA and protein expression levels of pro-inflammatory biomarkers IL-1β, IL-6, COX-2 and iNOS in LPS-stimulated murine RAW 264.7 macrophage cells. CZ and LE also significantly suppressed the NO production of LPS-stimulated RAW 264.7 cells. Additionally, CZ and LE suppressed the NF-κB luciferase activity in human HT-29 colon cancer cells. Both extracts also showed strong Nrf2-mediated antioxidant/Phase II detoxifying enzymes induction. CZ and LE induced NQO1, Nrf2, and UGT and antioxidant response element (ARE)-luciferase activity in human hepatoma HepG2 C8 cells. Using Nrf2 knockout [Nrf2 (−/−)] and Nrf2 wild-type (+/+) mice, LE and CZ showed Nrf2-dependent transactivation of Nrf2-mediated antioxidant and phase II detoxifying genes. In summary, CZ and LE possess strong inhibitory effects against NF-κB-mediated inflammatory as well as strong activation of the Nrf2-ARE-anti-oxidative stress signaling pathways, which would contribute to their overall health promoting pharmacological effects against diseases including cancer.

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“…2016; 5(3):e34363. 5 nutritional compounds capable of inhibiting the inflammatory process may be an important approach in preventing the progression of GERD (21). As shown here, treatment with B. oleracea extract decreased the severity of esophagitis without genotoxic and cytotoxic effects.…”

Section: Discussionmentioning

confidence: 60%

Evaluation of the Protective Effect of Brassica oleracea (L. var. acephala) in Rats with Surgically-Induced Gastroesophageal Reflux Disease

Wisnieski

Brito

Cosenza

et al. 2016

Thrita

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Background: Gastroesophageal reflux disease (GERD) is a common disorder that may result in esophageal cancer. Although proton pump inhibitors are the standard treatment for this illness, Brassica oleracea may provide new therapeutic possibilities. Objectives: We aimed to evaluate and compare the effects of the B. oleracea extract and the proton pump inhibitor omeprazole on esophageal complications arising from a surgically-induced GERD model in rats. In addition, we investigated possible associations between the frequency of DNA damage and esophageal histological alterations, as well as the genotoxic/anti-genotoxic and cytotoxic/anti-cytotoxic effects of B. oleracea and omeprazole. Methods: Rats with and without GERD were equally divided into groups to receive one of two the treatments, B. oleracea extract (500 mg/kg bw) or omeprazole (30 mg/kg bw), daily over the course of four weeks. A group of non-treated rats received water in the same circumstances. Micronucleus assay was used to assess DNA damage in blood and bone marrow cells. Results: Rats with GERD developed esophagitis and esophageal squamous cell carcinoma. B. oleracea and omeprazole-treated GERD rats presented significantly decreased inflammation in relation to non-treated GERD rats (P < 0.05). However, in rats without GERD, omeprazole significantly increased the frequencies of micronuclei and micronucleated cells as compared to the corresponding cell counts in non-treated rats (P = 0.04). Conclusions: B. oleracea demonstrated similar anti-inflammatory properties to omeprazole in rats with GERD. However, omeprazole also demonstrated genotoxic and cytotoxic effects in rats without GERD.

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Dietary Cancer Chemopreventive Agents – Targeting Inflammation and Nrf2 Signaling Pathway

Cited by 66 publications

References 86 publications

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Anti-inflammatory/Anti-oxidative Stress Activities and Differential Regulation of Nrf2-Mediated Genes by Non-Polar Fractions of Tea Chrysanthemum zawadskii and Licorice Glycyrrhiza uralensis

Evaluation of the Protective Effect of Brassica oleracea (L. var. acephala) in Rats with Surgically-Induced Gastroesophageal Reflux Disease

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