Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation

Hao, Qian; Wang, Min; Sun, Nuan‐Xin; Zhu, Cheng; Lin, Ying‐Min; Cui, Li; Liu, Fang; Zhu, Wenwen

doi:10.3892/or.2020.7495

Cited by 25 publications

(17 citation statements)

References 47 publications

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“…For example, in the absence of Nrf2 gene activity, the mitochondria-dependent protection by broccoli extract or sulforaphane from pulmonary injury is almost abolished [49], as is the PI3K-AKT-dependent protection by Withania from liver injury [99], or the hemooxygenase-1-dependent protection by curcumin or phenethyl isothiocyanate from inflammatory stress [50]. The extracellular-signal-regulated kinase (ERK) forms a signaling pathway together with Nrf2 [100,101], as does AMPK with Nrf2 [102]. Sirtuin-1 and Nrf2 represent another joint pathway induced by phytochemicals [103].…”

Section: Phytochemicals and Health-a Broader Perspectivementioning

confidence: 99%

Health Effects of Coffee: Mechanism Unraveled?

2020

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The association of habitual coffee consumption with a lower risk of diseases, like type 2 diabetes mellitus, chronic liver disease, certain cancer types, or with reduced all-cause mortality, has been confirmed in prospective cohort studies in many regions of the world. The molecular mechanism is still unresolved. The radical-scavenging and anti-inflammatory activity of coffee constituents is too weak to account for such effects. We argue here that coffee as a plant food has similar beneficial properties to many vegetables and fruits. Recent studies have identified a health promoting mechanism common to coffee, vegetables and fruits, i.e., the activation of an adaptive cellular response characterized by the upregulation of proteins involved in cell protection, notably antioxidant, detoxifying and repair enzymes. Key to this response is the activation of the Nrf2 (Nuclear factor erythroid 2-related factor-2) system by phenolic phytochemicals, which induces the expression of cell defense genes. Coffee plays a dominant role in that regard because it is the major dietary source of phenolic acids and polyphenols in the developed world. A possible supportive action may be the modulation of the gut microbiota by non-digested prebiotic constituents of coffee, but the available data are still scarce. We conclude that coffee employs similar pathways of promoting health as assumed for other vegetables and fruits. Coffee beans may be viewed as healthy vegetable food and a main supplier of dietary phenolic phytochemicals.

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Section: Phytochemicals and Health-a Broader Perspectivementioning

confidence: 99%

Health Effects of Coffee: Mechanism Unraveled?

2020

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“…Without doubt, the most controversial outcome of prolonged and gain-of-function Nrf2 activation concerns cancer progression [ [224] , [225] , [226] ]. It is well established that cytoprotection elicited through Nrf2 activation is important for the suppression of carcinogenesis in the first instance [ [227] , [228] , [229] , [230] ]. However, Nrf2 activity in aggressively malignant cells promotes tumorigenesis and metastasis [ 228 , [231] , [232] , [233] ], increases resistance to platinum-based chemotherapy [ 224 , [234] , [235] , [236] , [237] ] and has been associated with overall poorer prognosis [ 238 ].…”

Section: Balancing the Argument: Could Too Much Nrf2 Be Detrimental?mentioning

confidence: 99%

Targeting Nrf2 for the treatment of Duchenne Muscular Dystrophy

et al. 2021

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Imbalances in redox homeostasis can result in oxidative stress, which is implicated in various pathological conditions including the fatal neuromuscular disease Duchenne Muscular Dystrophy (DMD). DMD is a complicated disease, with many druggable targets at the cellular and molecular level including calcium-mediated muscle degeneration; mitochondrial dysfunction; oxidative stress; inflammation; insufficient muscle regeneration and dysregulated protein and organelle maintenance. Previous investigative therapeutics tended to isolate and focus on just one of these targets and, consequently, therapeutic activity has been limited. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor that upregulates many cytoprotective gene products in response to oxidants and other toxic stressors. Unlike other strategies, targeted Nrf2 activation has the potential to simultaneously modulate separate pathological features of DMD to amplify therapeutic benefits. Here, we review the literature providing theoretical context for targeting Nrf2 as a disease modifying treatment against DMD.

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“…Regarding these reports, the ingestion of Nrf2-activating phytochemicals including SFN could be harmful to colorectal cancer patients carrying the WT p53 gene. However, other studies have reported that SFN increases the nuclear translocation of Nrf2, inhibits cell proliferation and colony formation, and induces apoptosis in colon cancer HT-29 and SW480 cells [ 136 ].…”

Section: Regulation Of Nrf2/keap1 By Phytochemicals In Colorectal Cancermentioning

confidence: 99%

Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals

2021

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Colorectal cancer still has a high incidence and mortality rate, according to a report from the American Cancer Society. Colorectal cancer has a high prevalence in patients with inflammatory bowel disease. Oxidative stress, including reactive oxygen species (ROS) and lipid peroxidation, has been known to cause inflammatory diseases and malignant disorders. In particular, the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. Nrf2 was first found in the homolog of the hematopoietic transcription factor p45 NF-E2, and the transcription factor Nrf2 is a member of the Cap ‘N’ Collar family. KEAP1 is well known as a negative regulator that rapidly degrades Nrf2 through the proteasome system. A range of evidence has shown that consumption of phytochemicals has a preventive or inhibitory effect on cancer progression or proliferation, depending on the stage of colorectal cancer. Therefore, the discovery of phytochemicals regulating the Nrf2/KEAP1 axis and verification of their efficacy have attracted scientific attention. In this review, we summarize the role of oxidative stress and the Nrf2/KEAP1 signaling pathway in colorectal cancer, and the possible utility of phytochemicals with respect to the regulation of the Nrf2/KEAP1 axis in colorectal cancer.

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Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation

Cited by 25 publications

References 47 publications

Health Effects of Coffee: Mechanism Unraveled?

Health Effects of Coffee: Mechanism Unraveled?

Targeting Nrf2 for the treatment of Duchenne Muscular Dystrophy

Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals

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