Anticarcinogen

About: Anticarcinogen is a research topic. Over the lifetime, 251 publications have been published within this topic receiving 28870 citations. The topic is also known as: Anticarcinogenic Drugs & Anti-Carcinogenic Agents.

Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

Abstract: Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

Dietary carcinogens and anticarcinogens Oxygen radicals and degenerative diseases

Abstract: The human diet contains a great variety of natural mutagens and carcinogens, as well as many natural antimutagens and anticarcinogens. Many of these mutagens and carcinogens may act through the generation of oxygen radicals. Oxygen radicals may also play a major role as endogenous initiators of degenerative processes, such as DNA damage and mutation (and promotion), that may be related to cancer, heart disease, and aging. Dietary intake of natural antioxidants could be an important aspect of the body’s defense mechanism against these agents. Many antioxidants are being identified as anticarcinogens. Characterizing and optimizing such defense systems may be an important part of a strategy of minimizing cancer and other age-related diseases.

Expression of Cyclooxygenase-1 and -2 in Human Colorectal Cancer

Abstract: Several studies indicate that nonsteroidal anti-inflammatory drugs including indomethacin, aspirin, sulindac, and piroxicam reduce the risk of colon cancer. Furthermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) enzyme were shown to inhibit the development of colon cancer in animal models of carcinogenesis. Non-steroidal anti-inflammatory drugs inhibit the enzymatic activity of both the constitutive (COX-1) and inducible (COX-2) isoforms of COX enzyme. We have investigated the expression of COX-1 and COX-2 polypeptides in human colon cancer tissues using immunohistochemistry. Enhanced COX-2 expression was observed in colon cancer tissues from 15 subjects with clinically diagnosed colorectal cancer. Marked COX-2 expression was observed in cancer cells, inflammatory cells, vascular endothelium, and fibroblasts of the lesional tissues compared with the nonlesional and normal colon tissues. The extent and intensity of the immunoreactive COX-2 in cancer cells was much greater than that of the other cell types. In contrast, the expression of COX-1 polypeptide was weak in both normal and cancerous specimens. These data suggest that the enhanced expression of the COX-2 gene in colon cancer tissues may contribute to the enhanced synthesis of prostaglandin E2 by the colon cancer tissues. Enhanced expression of COX-2 may play a role in the pathogenesis of colon cancer. Furthermore, selective inhibition of COX-2 may prove to be more efficacious in the retardation of colon cancer development.

Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates.

Abstract: Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl)butane] was recently isolated from one variety of broccoli as the major and very potent inducer of phase 2 detoxication enzymes in murine hepatoma cells in culture Since phase 2 enzyme induction is often associated with reduced susceptibility of animals and their cells to the toxic and neoplastic effects of carcinogens and other electrophiles, it was important to establish whether sulforaphane could block chemical carcinogenesis In this paper we report that sulforaphane and three synthetic analogues, designed as potent phase 2 enzyme inducers, block the formation of mammary tumors in Sprague-Dawley rats treated with single doses of 9,10-dimethyl-1,2-benzanthracene The analogues are exo-2-acetyl-exo-6-isothiocyanatonorbornane, endo-2-acetyl-exo-6-isothiocyanatonorbornane, and exo-2-acetyl-exo-5-isothiocyanatonorbornane When sulforaphane and exo-2-acetyl-exo-6-isothiocyanatonorbornane were administered by gavage (75 or 150 mumol per day for 5 days) around the time of exposure to the carcinogen, the incidence, multiplicity, and weight of mammary tumors were significantly reduced, and their development was delayed The analogues endo-2-acetyl-exo-6-isothiocyanatonorbornane and exo-2-acetyl-exo-5-isothiocyanatonorbornane were less potent protectors Thus, a class of functionalized isothiocyanates with anticarcinogenic properties has been identified These results validate the thesis that inducers of phase 2 enzymes in cultured cells are likely to protect against carcinogenesis

Cancer chemopreventive activity of resveratrol.

Abstract: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit carcinogen-induced preneoplastic lesion formation in mouse mammary organ culture and tumorigenesis in the two-stage mouse skin model. Cancer chemopreventive potential was also suggested in various assays reflective of the three major stages of carcinogenesis. Anti-initiation activity was indicated by its antioxidant and antimutagenic effects, inhibition of the hydroperoxidase function of cyclooxygenase (COX), and induction of phase II drug-metabolizing enzymes. Antipromotion activity was indicated by antiinflammatory effects, inhibition of production of arachidonic acid metabolites catalyzed by either COX-1 or COX-2, and chemical carcinogen-induced neoplastic transformation of mouse embryo fibroblasts. Antiprogression activity was demonstrated by its ability to induce human promyelocytic leukemia (HL-60) cell differentiation. Moreover, pretreatment of mouse skin with resveratrol significantly counteracted 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress, as evidenced by numerous biochemical responses. Resveratrol reduced the generation of hydrogen peroxide, and normalized levels of myeloperoxidase and oxidized-glutathione reductase activities. It also restored glutathione levels and superoxide dismutase activity. As judged by the reverse transcriptase-polymerase chain reaction, resveratrol selectively inhibited TPA-induced expression of c-fos and transforming growth factor-beta 1 (TGF-beta 1), but did not affect other TPA-induced gene products including COX-1, COX-2, c-myc, c-jun, and tumor necrosis factor-alpha. These data indicate that resveratrol may interfere with reactive oxidant pathways and/or modulate the expression of c-fos and TGF-beta 1 to inhibit tumorigenesis in mouse skin. As reported herein, in addition to the activities described above, resveratrol inhibited the de novo formation of inducible nitric oxide synthase (iNOS) in mouse macrophages stimulated with lipopolysaccharide. This finding suggests an additional mechanism by which resveratrol may function as a cancer chemopreventive agent.