The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Increased Susceptibility of Nrf2 Knockout Mice to Colitis-Associated Colorectal Cancer
Open accessPublished version of a preprint
Abstract
The nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting various tissues against inflammation, which is a potential risk factor for colorectal and other cancers. Our previously published mouse model work showed that Nrf2 helps protect against dextran sulfate sodium (DSS)-induced colitis/inflammation, and others have shown that Nrf2 helps protect against inflammation-associated colorectal carcinogenesis (aberrant crypt foci). The present study extended these important earlier findings by exploring the role of Nrf2 in colitis-associated colorectal cancer in a mouse model involving azoxymethane/DSS-induced colorectal carcinogenesis in Nrf2 knockout mice. Azoxymethane/DSS-treated Nrf2 knockout mice had increased incidence, multiplicity, and size of all colorectal tumors, including adenomas, versus treated wild-type (WT) mice, and the proportion of tumors that were adenocarcinoma was much higher in knockout (80%) versus WT (29%) mice. Compared with WT mice, knockout mice also had increased markers of inflammation in tumor tissue (cyclooxygenase-2 and 5-lipoxygenase expressions and prostaglandin E(2) and leukotriene B(4) levels) and in inflamed colonic mucosa (nitrotyrosine expression), supporting the association of knockout mouse tumor formation with inflammation. The phase II detoxifying/antioxidant enzymes NAD(P)H-quinone reductase 1 and UDP-glucurosyltransferase 1A1 were elevated in the normal mucosa of WT, but not Nrf 2 knockout, mice treated with azoxymethane/DSS. Our findings show that Nrf2 plays a critical role in protecting against inflammation-associated colorectal cancer.
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“Our data show that tissue and plasma from Nrf2KO mice present higher levels of inflammation at 4 month of age (measured by the cytokine levels), corroborating previous reports (Ishii et al., 2005; Khor et al., 2008).”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Khor et al., 2008
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Citations
Cites
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Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028 · cited 2×
“Our present study joins other recent studies (6, 15, 16), including our study showing that Nrf2deficient mice were more susceptible to DSS-induced colitis (6), in suggesting that Nrf2 may play a central role in regulating inflammation because Nrf2 is an integral regulator of detoxification and antioxidation mechanisms.”
BackgroundResultGenetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice
Rangasamy, T., Cho, C. Y., Thimmulappa, R. K., Zhen, L., Srisuma, S., Kensler, T. W., Yamamoto, M. P., Petrache, I., Tuder, R. M., & Biswal, S. S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21146 · Cited by 993
Prostaglandins, Arachidonic Acid, and Inflammation
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Nrf2-Deficient Mice Have an Increased Susceptibility to Dextran Sulfate Sodium–Induced Colitis
Khor, T. O., Huang, M., Kwon, K. H., Chan, J. Y., Reddy, B. S., & Kong, A. T. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-3562 · Cited by 530
Self-citationUlcerative colitis and colorectal cancer
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Miyamoto, S. (2026) · Springer eBooks · doi:10.1007/978-981-95-7068-3_39
Giri, M., Arya, S., Grover, M., Yadav, D., Chatterjee, S., & Rath, S. K. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02322-2
Benjamin, M., Sharawat, S. K., & Chopra, A. (2026) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-026-00869-y
Pianka, M.-L., Zhang, X., & Stein‐Thoeringer, C. K. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2718561
Rahimi, K., Rezaie, A., Hosseini, H., Khajehian, B., Hayati, M., & Hajiuni, M. (2026) · Advances in Redox Research · doi:10.1016/j.arres.2026.100200
BindingDB (2021) · UC San Diego · doi:10.7270/q26h4mw8
Role of Nutraceuticals on Nrf2 and Its Implication in Cancer Prevention
Saw, C. L. L., & Kong, A. T. (2011) · Springer eBooks · doi:10.1007/978-94-007-2630-7_4
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Metadata
- Authors
- Khor, T. O., Huang, M.-T., Prawan, A., Liu, Y., Hao, X., Yu, S., Cheung, W. K. L., Chan, J. Y., Reddy, B. S., Yang, C. S., & Kong, A.-N.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Kong, Ah-Ng
- Venue
- Cancer Prevention Research
- Published
- 2008-07-25
- Volume
- 1
- Issue
- 3
- Pages
- 187-191
- ISSN
- 1940-6207 (ISSN-L)
- 1940-6215
- PMC
- PMC3580177
- OpenAlex
- W2141004419
- Cited by
- 306
- References
- 22
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 9 · 2023: 17 · 2022: 18 · 2021: 10 · 2020: 23 · 2019: 28 · 2018: 21 · 2017: 34 · 2016: 22 · 2015: 22 · 2014: 18 · 2013: 16 · 2012: 16
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Prevention Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA073674)
- National Institute of Environmental Health Sciences (P30ES005022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- Nrf2, colitis-associated colorectal cancer, Nrf2 knockout mice, inflammation-associated carcinogenesis, colorectal adenoma, cyclooxygenase-2, 5-lipoxygenase, prostaglandin E2, leukotriene B4, nitrotyrosine, UDP-glucuronosyltransferase 1A1, phase II enzymes, antioxidant defense
- MeSH terms
- Adenocarcinoma, Adenoma, Animals, Azoxymethane, Colitis, Male, Mice, Inbred C57BL, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Dextran Sulfate, Mice, Knockout, Cytoprotection, Genetic Predisposition to Disease, NF-E2-Related Factor 2, Mice, Cyclooxygenase 2
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