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

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 743
Author(s):  
Da-Young Lee ◽  
Moon-Young Song ◽  
Eun-Hee Kim
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Inflammatory Diseases ◽  
Negative Regulator ◽  
Related Factor ◽  
Cancer Society ◽  
Incidence And Mortality

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.

scholarly journals The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

2018 ◽  
Vol 19 (12) ◽  
pp. 3711 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Daniel Sur ◽  
Calin Cainap ◽  
Simona Visan ◽  
Daniel Cruceriu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Cancer Progression ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Cancer Management ◽  
Incidence And Mortality ◽  
The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

scholarly journals Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3208 ◽  
Author(s):  
Fabiane Valentini Francisqueti-Ferron ◽  
Artur Junio Togneri Ferron ◽  
Jéssica Leite Garcia ◽  
Carol Cristina Vágula de Almeida Silva ◽  
Mariane Róvero Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Factor ◽  
Future Research ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Age Related ◽  
Basic Concepts

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

scholarly journals The Expanding Role of MT1-MMP in Cancer Progression

2019 ◽  
Vol 12 (2) ◽  
pp. 77 ◽  
Author(s):  
Anna M. Knapinska ◽  
Gregg B. Fields
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Cancer Progression ◽  
Negative Regulator ◽  
Fibrillar Collagen ◽  
Biological Functions ◽  
Complete Mapping ◽  
Membrane Type

For over 20 years, membrane type 1 matrix metalloproteinase (MT1-MMP) has been recognized as a key component in cancer progression. Initially, the primary roles assigned to MT1-MMP were the activation of proMMP-2 and degradation of fibrillar collagen. Proteomics has revealed a great array of MT1-MMP substrates, and MT1-MMP selective inhibitors have allowed for a more complete mapping of MT1-MMP biological functions. MT1-MMP has extensive sheddase activities, is both a positive and negative regulator of angiogenesis, can act intracellularly and as a transcription factor, and modulates immune responses. We presently examine the multi-faceted role of MT1-MMP in cancer, with a consideration of how the diversity of MT1-MMP behaviors impacts the application of MT1-MMP inhibitors.

Sa2050 The Role of Transcription Factor GFI1 in Colorectal Cancer Progression and Metastasis

2016 ◽  
Vol 150 (4) ◽  
pp. S439-S440
Author(s):  
Min-Shan Chen ◽  
Yuan-Hung Lo ◽  
Xi Chen ◽  
Christopher S. Williams ◽  
Noah F. Shroyer
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Colorectal Cancer Progression

scholarly journals The role of Snail1 transcription factor in colorectal cancer progression and metastasis

2015 ◽  
Vol 4 ◽  
pp. 265-270 ◽  
Author(s):  
Marlena Brzozowa ◽  
Marek Michalski ◽  
Grzegorz Wyrobiec ◽  
Adam Piecuch ◽  
Anna Dittfeld ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Colorectal Cancer Progression

scholarly journals Nrf2 activation does not affect adenoma development in a mouse model of colorectal cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Elena V. Knatko ◽  
Cecilia Castro ◽  
Maureen Higgins ◽  
Ying Zhang ◽  
Tadashi Honda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenomas ◽  
Negative Regulator ◽  
Related Factor ◽  
Early Stages ◽  
Nrf2 Activation ◽  
One Carbon Metabolism ◽  
Nrf2 Protein ◽  
Transcription Factor Nuclear Factor

AbstractTranscription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) and its main negative regulator, Kelch-like ECH associated protein 1 (Keap1), are at the interface between redox and intermediary metabolism. Nrf2 activation is protective in models of human disease and has benefits in clinical trials. Consequently, the Keap1/Nrf2 protein complex is a drug target. However, in cancer Nrf2 plays a dual role, raising concerns that Nrf2 activators may promote growth of early neoplasms. To address this concern, we examined the role of Nrf2 in development of colorectal adenomas by employing genetic, pharmacological, and metabolomic approaches. We found that colorectal adenomas that form in Gstp−/−: ApcMin/+ mice are characterized by altered one-carbon metabolism and that genetic activation, but not disruption of Nrf2, enhances these metabolic alterations. However, this enhancement is modest compared to the magnitude of metabolic differences between tumor and peri-tumoral tissues, suggesting that the metabolic changes conferred by Nrf2 activation may have little contribution to the early stages of carcinogenesis. Indeed, neither genetic (by Keap1 knockdown) nor pharmacological Nrf2 activation, nor its disruption, affected colorectal adenoma formation in this model. We conclude that pharmacological Nrf2 activation is unlikely to impact the early stages of development of colorectal cancer.

Redox regulation of lung inflammation: role of NADPH oxidase and NF-κB signalling

2007 ◽  
Vol 35 (5) ◽  
pp. 1151-1155 ◽  
Author(s):  
H. Yao ◽  
S.-R. Yang ◽  
A. Kode ◽  
S. Rajendrasozhan ◽  
S. Caito ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Redox Regulation ◽  
Inflammatory Diseases ◽  
Complex Mixture ◽  
Nuclear Factor Κb ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Nuclear Factor

Regulation of reduction/oxidation (redox) state is critical for cell viability, activation, proliferation and organ function, and imbalance of oxidant/antioxidant balance is implicated in various chronic respiratory inflammatory diseases, such as asthma, pulmonary fibrosis and chronic obstructive pulmonary disease. CS (cigarette smoke) is a complex mixture of various noxious gases and condensed tar particles. These components elicit oxidative stress in lungs by continuous generation of ROS (reactive oxygen species) and various inflammatory mediators. In the present review, we have discussed the role of oxidative stress in triggering the inflammatory response in the lungs in response to CS by demonstrating the role of NADPH oxidase, redox-sensitive transcription factors, such as pro-inflammatory NF-κB (nuclear factor κB) and antioxidant Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), as well as HDAC (histone deacetylase) in pro-inflammatory cytokine release by disruption of HDAC–RelA/p65 NF-κB complex.

scholarly journals Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana F. Saldanha ◽  
Viviane de O. Leal ◽  
Peter Stenvinkel ◽  
José Carlos Carraro-Eduardo ◽  
Denise Mafra
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Related Factor ◽  
Nuclear Factor ◽  
Family Protein ◽  
Nrf2 Activation ◽  
And Oxidative Stress

Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promotetranscription factor nuclear factor-erythroid 2-related factor 2(Nrf2) activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB) activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD), are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

scholarly journals Antioxidants Promote Intestinal Tumor Progression in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 241
Author(s):  
Zhiyuan V. Zou ◽  
Kristell Le Gal ◽  
Ahmed E. El Zowalaty ◽  
Lara E. Pehlivanoglu ◽  
Viktor Garellick ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Tumor Progression ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Intestinal Tumor ◽  
Adenomatous Polyposis ◽  
Intestinal Tumors ◽  
The Impact

Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.

scholarly journals Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Carmen Griñan-Lison ◽  
Jose L. Blaya-Cánovas ◽  
Araceli López-Tejada ◽  
Marta Ávalos-Moreno ◽  
Alba Navarro-Ocón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chemopreventive Agents ◽  
Low Degree ◽  
Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

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