• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.92-93
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• 2003

Chemoprevention refers to the use of agents to inhibit, reverse, or retard tumorigenesis. Numerous phytochemicals present in edible plants have been reported to interfere with a specific stage of the carcinogenic process. Some antioxidative and anti-inflammatory substances derived from dietary or medicinal plants exert chemopreventive properties by targeting intracellular signaling molecules or events.(omitted)

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.1-15
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• 2005

Cancer is still a major global health concern even after an everlasting strive in conquering this dread disease. Emphasis is now given to chemoprevention to reduce the risk of cancer and also to improve the quality of life among cancer afflicted individuals. Recent progress in molecular biology of cancer has identified key components of the cellular signaling network, whose functional abnormality results in undesired alterations in cellular homeostasis, creating a cellular microenvironment that favors premalignant and malignant transformation. Multiple lines of evidence suggest an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to cancer. In response to oxidative/pro-inflammatory stimuli, turning on unusual signaling arrays mediated through diverse classes of kinases and transcription factors results in aberrant expression of COX-2. Population-based as well as laboratory studies have explored a broad spectrum of chemopreventive agents including selective COX-2 inhibitors and a wide variety of anti-inflammatory phytochemicals, which have been shown to target cellular signaling molecules as underlying mechanisms of chemoprevention. Thus, unraveling signaling pathways regulating aberrant COX-2 expression and targeted blocking of one or more components of those signal cascades may be exploited in searching chemopreventive agents in the future.

• Toxicological Research
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• v.23 no.3
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• pp.207-214
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• 2007

Chronic oxidative stress produced by exposure to environmental chemicals or pathophysiological states can lead animals to aging, carcinogenesis and degenerative diseases. Indirect antioxidative mechanisms, in which natural or synthetic agents are used to coordinately induce the expression of cellular antioxidant capacity, have been shown to protect cells and organisms from oxidative damages. Electrophile and free radical detoxifying enzymes, which were originally identified as the products of genes induced by cancer chemopreventive agents, are members of this protective system. The NFE2 family transcription factor Nrf2 was found to govern expression of these detoxifying enzymes, and screening for Nrf2-regulated genes has identified many gene categories involved in maintaining cellular redox potential and protection from oxidative damage as Nrf2 downstream genes. Further, studies using Nrf2-deficient mice revealed that these mutant mice showed more susceptible phenotypes towards exposure to environmental chemicals/carcinogens and in oxidative stress related disease models. With the finding that cancer chemopreventive efficacy of indirect antioxidants (enzyme inducers) is lost in the absence of Nrf2, a central role of Nrf2 in the antioxidative protective system has been firmly established. Promising results from cancer prevention clinical trials using enzyme inducers propose that pharmacological interventions that modulate Nrf2 can be an effective strategy to protect tissues from oxidative damage.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.32-38
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• 2010

The aim of this study was to evaluate the effect of galangin towards hydrogen peroxide-induced DNA damage. The calf thymus DNA and Chinese Hamster Lung (CHL) cells were used to measure 8-hydroxy-2'-deoxyguanosine(8-OH2'dG) as an indicator of DNA oxidative damage using high performance liquid chromatography with electrochemical detection. Hydrogen peroxide in the presence of Fe(II) ion induced the formation of 8-OH2'dG in both calf thymus DNA and CHL cells. The DNA damage effects were enhanced by increasing the concentration of Fe(II) ion and inhibited by galangin. In the single cell gel electrophoresis (Comet assay), galangin and dl-a-tocopherol showed an inhibitory effect in CHL on hydrogen peroxide induced DNA single strand breaks. Galangin showed more potent activity than dl-$\alpha$-tocopherol under our experimental conditions. These results indicate that galangin can modify the action mechanisms of the oxidative DNA damage and may act as chemopreventive agents against oxidative stress.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.101-101
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• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

• Korean Journal of Pharmacognosy
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• v.38 no.1
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• pp.95-99
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• 2007

In order to find novel cancer chemopreventive agents, quinone reductase (QR) inductive activity of methanol extract of herbal medicines was examined using murine hepatoma, hepa1c1c7 cells. QR has been used as an anticarcinogenic marker enzyme in cancer chemoprevention study. The methanol extract of Alpinia officinarum (Zingiberace) showed showed significantly strong quinone reductase inductive activity compared to the control group. The methanol extract of Alpinia officinarum was successively fractionated with various solvents according to polarity. Hexane, ethyl acetate, buthanol and water fractions were obtained and theirs activities were assessed. The QR inductive effect was moved to the ethyl acetate fraction and was highly increased. The CD (concentration required to double the specific activity of QR) value of ethyl acetate fraction was 8.6 ${\mu}g/mL$. Alpinia officinarum also showed strong antioxidant activity. These results suggest that Alpinia officinarum can be developed as cancer chemopreventive agent.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.501-508
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• 2007

Proanthocyanidins (PACs), also named condensed tannins, are polymers of flavan-3-ols such as (+ )-(gallo)catechin and (-)-epi(gallo)catechin. A proper analysis of the PACs, with difficult challenges due to their complex structures, is crucial in studies of cancer chemoprevention. Cancer is a leading cause of mortality around the world. Many experimental studies have shown that dietary PACs are potential chemopreventive agents that block or suppress against multistage carcinogenesis in both in vitro and in vivo models. Cancer chemoprevention by dietary PACs has been shown effective through different mechanisms of action such as antioxidant, apoptosis-inducing, and enzyme inhibitory activities. Good sources of dietary PACs are nuts, fruits, beans, chocolate, fruit juice, red wine, and green tea. The chemopreventive potential of dietary PACs should be considered together with their bioavailability in humans. The safety issues regarding carcinogenesis and gastrointestinal disorder are also reviewed.

• Food Science and Biotechnology
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• v.17 no.3
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• pp.613-622
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• 2008

Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at $100\;{\mu}g/mL$ by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production in a dose-dependant manner in $5-20\;{\mu}g/mL$. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and $PGE_2$ production.

• Food Science and Preservation
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• v.8 no.2
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• pp.213-216
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• 2001

Chemoprevetive effect of Saururus Chinensis (Lour.) Bail water extract on several tumor cells and Chinese hamster V79 cells were investigated. The water extracts of Saururus Chinensis (Lour.) Bail showed a higher cytotoxicity effect on the human histiocytic leukemia cells(U937) and protective effects against the cytotoxicity of H$_2$O$_2$. These results suggest that Saururus Chinensis (Lour.) Bail may useful as potential soures of chemopreventive and antioxidative agents.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.177-178
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• 2002

Chemoprevention, one of the most innovative and promising areas of cancer research, refers to the prevention of cancer through pharmacologic or nutritional intervention. Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as inflammation. Inappropriate up-regulation of COX-2 is implicated in the pathophysiology of certain types of human cancers. (omitted)