Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals.
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.
Murakami
Akira
A
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. cancer@kais.kyoto-u.ac.jp
Ohigashi
Hajime
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D001592:Benzyl Alcohols; D003474:Curcumin / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005502:Food; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D008070:Lipopolysaccharides / Q000378:metabolism; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D001592:Benzyl Alcohols; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012717:Sesquiterpenes; D013729:Terpenes; C403304:zerumbone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D003474:Curcumin; D015232:Dinoprostone; C047948:1'-acetoxychavicol acetate