Targeting NOX, iNOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals

Murakami, Akira; Ohigashi, Hajime

doi:10.1002/ijc.23161

Cited by 478Inflammatory mediators and NSAID effectsNatural Compounds in Disease TreatmentGenomics, phytochemicals, and oxidative stress

Targeting NOX, iNOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals

Murakami, Akira, Ohigashi, Hajime·2007·International Journal of Cancer

DOI 10.1002/ijc.23161

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Abstract

Biological, biochemical and physical stimuli activate inflammatory leukocytes, such as macrophages, resulting in induction and synthesis of proinflammatory proteins and enzymes, together with free radicals, as innate immune responses. On the other hand, chronic and dysregulated activation of some inducible enzymes, including NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, have been shown to play pivotal roles in the development of certain inflammatory diseases such as oncogenesis. While the use of synthetic agents, especially those targeting molecules, is an attractive and reasonable approach to prevent carcinogenesis, it should be noted that traditional herbs and spices also exist along with their active constituents, which have been demonstrated to disrupt inflammatory signal transduction pathways. In this mini-review, the molecular mechanisms of activation or induction of NOX, iNOS and COX-2, as well as some food phytochemicals with marked potential to regulate those key inflammatory molecules, are highlighted. For example, 1'-acetoxychavicol acetate, which occurs in the rhizomes of the subtropical Zingiberaceae plant, has been shown to attenuate NOX-derived superoxide generation in macrophages, as well as lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production through the suppression of iNOS and COX-2 synthesis, respectively. Notably, this phytochemical has exhibited a wide range of cancer prevention activities in several rodent models of inflammation-associated carcinogenesis. Herein, the cancer preventive potentials of several food phytochemicals targeting the induction of NOX, iNOS and COX-2 are described.

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Two COX isoforms exist; COX-1 is constitutive, whereas COX-2 protein is only slightly expressed in most normal mammalian tissues and is induced by physical, chemical, and biological stimuli including UV light, dioxin, and LPS.
“Two isoforms of COX, COX-1 and COX-2, have been reported. COX-1 is a constitutive enzyme whilst COX-2 protein is only slightly expressed in most normal mammalian tissues in response to physical, chemical and biological stimuli, including UV light exposure, dioxin and LPS (lipopolyssacharide) insult [96].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [96]

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Authors: Murakami, A., & Ohigashi, H.
Affiliations: Kyoto University (JP)
Corresponding author: Murakami, Akira
ORCID: Murakami, Akira
Venue: International Journal of Cancer
Publisher: Wiley
Published: 2007-09-24
Volume: 121
Issue: 11
Pages: 2357-2363
ISSN: 0020-7136 (ISSN-L)
1097-0215
DOI: 10.1002/ijc.23161
OpenAlex: W2071705097
Cited by: 478
References: 122
Citations by year: 2026: 14 · 2025: 22 · 2024: 29 · 2023: 20 · 2022: 29 · 2021: 26 · 2020: 31 · 2019: 23 · 2018: 23 · 2017: 47 · 2016: 24 · 2015: 30 · 2014: 29 · 2013: 31 · 2012: 23
FWCI: 1.95
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: International Journal of Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords: NADPH oxidase, inducible nitric oxide synthase, cyclooxygenase-2, dietary phytochemicals, chemoprevention, inflammation-associated carcinogenesis, macrophages, 1'-acetoxychavicol acetate, Zingiberaceae, superoxide production, nitric oxide, prostaglandin E2
MeSH terms: Animals, Anti-Inflammatory Agents, Non-Steroidal, Benzyl Alcohols, Curcumin, Enzyme Induction, Enzyme Inhibitors, Food, Humans, Inflammation, Lipopolysaccharides, Plant Extracts, Sesquiterpenes, Terpenes, Dinoprostone, Anticarcinogenic Agents, NADPH Oxidases, Cyclooxygenase 2, Nitric Oxide Synthase Type II

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Targeting NOX, iNOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals

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