Mkp-1 is required for chemopreventive activity of butylated hydroxyanisole and resveratrol against colitis-associated colon tumorigenesis

Zheng, Zhaohong; Chen, Yeru; Huang, Jianan; Deng, Hong; Tang, Xiuwen; Wang, Xiu Jun

doi:10.1016/j.fct.2019.02.044

Cited by 29 publications

(17 citation statements)

References 44 publications

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“…In our recent work, we addressed the interplay between MKP-1 and Nrf2 in cytoprotective actions in mice liver and colon [24–26]. We have reported a new physiological role of MKP-1 in the maintenance of redox homeostasis in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…Our studies showed that direct interaction of the DIDLID motif of NRF2 with Mkp-1 leads to increased Nrf2 stability and positive regulation of the Nrf2 pathway. A role of the Mkp-1/Nrf2 axis in limiting inflammation in murine colitis has also been demonstrated [25, 26]. However, it is not known whether MKP-1 could cross-talk with Nrf2 to support an oncogenic program that increases cell proliferation and drug resistance in NSCLC cells.…”

Section: Introductionmentioning

confidence: 99%

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Interplay of MKP-1 and Nrf2 drives tumor growth and drug resistance in non-small cell lung cancer

Wang

Liu

Chi

et al. 2019

Aging

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Alterations in KEAP1/ NF-E2 p45-related factor 2 (NFE2L2/Nrf2) signaling pathway have been reported in 23% lung adenocarcinoma patients, suggesting that deregulation of the pathway is a major cancer driver. Here we report that mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) drives tumor growth and drug resistance by up regulating transcription factor Nrf2. In non-small cell lung cancer (NSCLC) cells and xenografts, MKP-1 knockdown triggered the down-regulation of the metabolic enzymes and cytoprotective proteins, which are the target genes of Nrf2. Consequently, the cell growth was markedly inhibited with decrease of tumor metabolisms and GSH contents. Moreover, MKP-1 silencing sensitized NSCLC cells to cisplatin treatment. Mechanistically, MKP-1 inhibited the ubiquitylation of Nrf2 via a direct interaction with the transcription factor. Nrf2 was hence stabilized and its transcriptional program was activated. Notably, Nrf2 elevated MKP-1 expression at transcriptional level. In human lung adenoma tumor samples, high levels of expression of MKP-1, Nrf2, and its target gene heme oxygenase 1 were closely correlated. Thus, MKP-1 and Nrf2 form a forward feedback loop in lung cancer cells, which stabilizing and activating Nrf2 to promote anabolic metabolism and GSH biosynthesis. This study uncovers a novel role of MKP-1 in the malignant evolution of cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interplay of MKP-1 and Nrf2 drives tumor growth and drug resistance in non-small cell lung cancer

Wang

Liu

Chi

et al. 2019

Aging

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“…While, oral administration of resveratrol failed to protect mice from chemically induced lung carcinogenesis [34]. Moreover, dietary suppression of dextran sulfate sodium (DSS)-associated tumorigenesis using resveratrol (300 ppm) supplementation for one week before the treatment was markedly exhibited in BALB/c background wild-type mice but not in Mkp-1−/− mice on the C57BL/6 background [35]. Additionally, the mitogen-activated protein kinase phosphatase 1 (Mkp-1) is required in the protective role of the Nrf2 signaling pathway against colitis-associated tumorigenesis.…”

Section: Polyphenolsmentioning

confidence: 99%

Plant Natural Products: Promising Resources for Cancer Chemoprevention

Zhang

Zhao

et al. 2021

Molecules

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Cancer is a major factor threatening human health and life safety, and there is a lack of safe and effective therapeutic drugs. Intervention and prevention in premalignant process are effective ways to reverse carcinogenesis and prevent cancer from occurring. Plant natural products are rich in sources and are a promising source for cancer chemoprevention. This article reviews the chemopreventive effects of natural products, especially focused on polyphenols, flavonoids, monoterpene and triterpenoids, sulfur compounds, and cellulose. Meanwhile, the main mechanisms include induction of apoptosis, antiproliferation and inhibition of metastasis are briefly summarized. In conclusion, this article provides evidence for natural products remaining a prominent source of cancer chemoprevention.

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“…IHC of colon sections from mice was carried out using formalin-fixed paraffin-embedded tissue as described previously [47]. The semiquantitative results of IHC were based on the average value from three mice per group.…”

Section: Methodsmentioning

confidence: 99%

Synthetic Imine Resveratrol Analog 2-Methoxyl-3,6-Dihydroxyl-IRA Ameliorates Colitis by Activating Protective Nrf2 Pathway and Inhibiting NLRP3 Expression

Chen

Zheng

et al. 2019

Oxidative Medicine and Cellular Longevity

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Resveratrol (RSV) is a naturally occurring polyphenol that exhibits pleiotropic health benefits, including anticolitis and colon cancer-protective activity. Recently, we identified the novel imine RSV analog (IRA), 2-methoxyl-3,6-dihydroxyl-IRA 3,4,5,4-tetramethoxystilbene (C33), as a putative activator of nuclear factor erythroid 2-related factor 2 (Nrf2). The present study was designed to evaluate the ability of C33 to activate the Nrf2 signaling pathway and its anticolitis effect in comparison to RSV. The anticolitis action of C33 was assessed in a mouse model of colitis induced by dextran sulfate sodium (DSS). The effect of C33 on the Nrf2 signaling pathway was examined in vitro and in vivo. Compared to RSV, C33 triggered a more dramatic increase in the expression of genes downstream of Nrf2 in LS174T cells as well as in the small intestine and colon of wild-type (WT) mice. Correlated with its superior ability to activate the cytoprotective Nrf2 pathway, C33 was significantly better in ameliorating DSS-induced colitis by improving the inflammation score, as well as downregulating the markers of inflammation in WT mice. Moreover, induction of the NOD-like receptors family pyrin domain containing 3 (NLRP3) inflammasome by colitis was also significantly inhibited by the IRA. Nrf2 knockout completely abolished the effects of C33, indicating that Nrf2 is the important mechanistic target of C33 in vivo. In conclusion, the novel IRA, C33, has stronger anticolitis effects than RSV. Further studies are warranted to evaluate C33 as a potential therapeutic agent for inflammatory bowel disease and cancer chemoprevention.

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Mkp-1 is required for chemopreventive activity of butylated hydroxyanisole and resveratrol against colitis-associated colon tumorigenesis

Cited by 29 publications

References 44 publications

Interplay of MKP-1 and Nrf2 drives tumor growth and drug resistance in non-small cell lung cancer

Interplay of MKP-1 and Nrf2 drives tumor growth and drug resistance in non-small cell lung cancer

Plant Natural Products: Promising Resources for Cancer Chemoprevention

Synthetic Imine Resveratrol Analog 2-Methoxyl-3,6-Dihydroxyl-IRA Ameliorates Colitis by Activating Protective Nrf2 Pathway and Inhibiting NLRP3 Expression

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