• Title/Summary/Keyword: Cancer chemoprevention

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Cancer Chemoprevention by Dietary Phytochemicals: Rationale and Mechanisms (Dietary Phytochemical을 이용한 화학적 암에방과 그 작용 기전)

  • Surh, Young-Joon;Lee, Jong-Min
    • Environmental Mutagens and Carcinogens
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    • v.18 no.1
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    • pp.1-8
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    • 1998
  • Chemoprevention refers to the use of non-toxic chemical agents to prevent the neoplastic development by inhibiting, delaying, or reversing a multi-stage carcinogenesis. The primary goal of chemoprevention research is to identify or produce effective agents and strategies for clinical trials for applications to normal or high risk human populations. A large number of compounds have been tested for their possible chemopreventive activities, and it is of interest to note that many of them are naturally occurring substances. Thus, a variety of plant and vegetable constituents, particularly those included in our daily diet, have been found to possess substantial protective properties against experimental carcinogenesis. These substances, collectively known as dietary phytochemicals, exert their chemopreventive effects by influencing specific step(s) of multi-stage carcinogenesis: some inhibit metabolic activation or enhance detoxification of carcinogens, others interfere with covalent interactions between ultimate eloctrophilic carcinogens and the target cell DNA and still others may exert anti-promoting or anti-progressing effects. Mechanism-based interventions by use of safe dietary phytochemicals may provide one of the most practical and promising cancer chemopreventive strategies.

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A Novel Synthetic Compound, YH-1118, Inhibited LPS-Induced Inflammatory Response by Suppressing IκB Kinase/NF-κB Pathway in Raw 264.7 Cells

  • Yun, Chang Hyun;Jang, Eun Jung;Kwon, Soon Cheon;Lee, Mee-Young;Lee, Sangku;Oh, Sei-Ryang;Lee, Hyeong-Kyu;Ahn, Kyung-Seop;Lee, Ho-Jae
    • Journal of Microbiology and Biotechnology
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    • v.25 no.7
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    • pp.1047-1055
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    • 2015
  • For the search of a potent first-in-class compound to inactivate macrophages responsible for inflammatory responses, in the present study, we investigated the anti-nflammatory effects of YH-1118, a novel synthetic compound, in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line, Raw 264.7. YH-1118 inhibited LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression at both the protein and mRNA levels. The suppression of LPS-induced iNOS expression by YH-1118 was mediated via nuclear factor kappa B (NF-κB), but not activator protein-1 (AP-1) transcription factor. This was supported by the finding that YH-1118 attenuated the phosphorylation of inhibitor of κBα (IκBα) and nuclear translocation and DNA binding activity of NF-κB. Through the mechanisms that YH-1118 inhibited the activation of IκB kinases (IKKs), upstream activators of NF-κB, or p38 MAPK, YH-1118 significantly suppressed LPS-induced production of pro-inflammatory cytokines, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 (p < 0.05). In conclusion, our results suggest that YH-1118 inhibits LPS-induced inflammatory responses by blocking IKK and NF-κB activation in macrophages, and may be a therapeutic candidate for the treatment of various inflammatory diseases.

MECHANISMS AND APPLICATIONS OF NSAIDS IN THE CHEMOPREVENTION OF CANCER

  • Steele, Vernon E.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.27-27
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    • 2001
  • Significant evidence exists which demonstrates that inflammation predisposes and promotes the cancer process in humans. Chronic inflammation can induce cancer in a variety of organ sites, including bowel and lung. There is also firm evidence that induced cyclooxygenases and nitric oxide synthetases, prostaglandins, and inflammatory cytokines can promote and accelerate the carcinogenic process.(omitted)

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In Vitro Cancer Chemopreventive Activities of Polysaccharides from Soybeans Fermented with Phellinus igniarius or Agrocybe cylindracea

  • Shon, Yun-Hee;Nam, Kyung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.11 no.6
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    • pp.1071-1076
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    • 2001
  • Chemopreventive activities of polysaccharides from soybeans fermented with either Phellinus igniarius or Agrocybe cylindracea were investigated by measuring the induction of quinone reductase (QR), glutathione S-transferase (GST) activities, and glutathione (GSH) levels in the cell culture along with inhibition of polyamine biosynthesis. The polysaccharides from soybeans fermented with P. igniarius strongly (p<0.005) induced QR activity at all concentrations tested. The extract not only induced GST activity in a dose-dependent manner in the concentration range of 0.1-1.0 mg, but significantly induced GSH revels in cultured Hepa 1c1c7 cells with a maximal 1.4-fold increase at 0.1 mg. The polysaccharides from soybeans fermented with A. cylindracea were effective in inhibiting polyamine metabolism. These results suggest that polysaccharides from soybeans fermented with P. igniarius or A. cylindracea have cancer chemopreventive activities in in vitro models and, therefore, could be considered as potential agents for cancer chemoprevention.

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Tumor suppressor $p16^{INK4a}$ in Cancer

  • Lee, Mee-Hyun;Choi, Bu-Young;Surh, Young-Joon
    • Environmental Mutagens and Carcinogens
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    • v.25 no.3
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    • pp.87-96
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    • 2005
  • [ $p16^{INK4a}$ ] is a tumor suppressor that belongs to the INK4 family of the cyclin D-dependent kinases (cdk) inhibitors. It plays regulatory roles in cell proliferation and in tumorigenesis by interacting with Rb signaling. Abnormally elevated $p16^{INK4a}$ protein expression causes cell cycle arrest (G1/S transition) and loss of cyclin-cdk activity. In many cancers, $p16^{INK4a}$ is altered by mutation, deletion, and promoter methylation. This review summarizes the function of p16 as an important regulator of cancer pathobiology and a promising target fer developing cancer therapeutic and chemopreventive agents.

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Cancer Chemopreventive Potential of Procyanidin

  • Lee, Yongkyu
    • Toxicological Research
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    • v.33 no.4
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    • pp.273-282
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    • 2017
  • Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

Naturally-Occurring Glucosinolates, Glucoraphanin and Glucoerucin, are Antagonists to Aryl Hydrocarbon Receptor as Their Chemopreventive Potency

  • Razis, Ahmad Faizal Abdull;Noor, Noramaliza Mohd
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5801-5805
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    • 2015
  • As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several pathophysiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract

  • Sharma, Jyoti;Goyal, Pradeep K.
    • Journal of Ginseng Research
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    • v.39 no.3
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    • pp.265-273
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    • 2015
  • Background: Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticancer and antioxidative potential of Panax ginseng against chemical-induced skin carcinogenesis in mammals. Methods: Skin tumors were induced in Swiss albino mice by a single topical application of 7,12-dimethylbenz(a)anthracene ($100{\mu}g/100{\mu}L$ acetone) and, 2 wks later, promoted by repeated applications of croton oil (thrice in a wk in 1% acetone) till the end of the experiment (i.e., 16 wk). Hydroalcoholic ginseng root extract at a dose of 25 mg/kg body weight/d was orally administered at the periinitiation, postinitiation, and peri-post-initiation stages. Results: Ginseng root extract treatment caused a significant reduction in tumor incidence, cumulative number of tumors, tumor yield, and tumor burden, as compared to the 7,12-dimethylbenz(a)anthracene-croton oil-treated control group. Further, biochemical assays revealed a significant enhancement in the levels of reduced glutathione, superoxide dismutase, catalase, vitamin C, and total proteins but a significant reduction in lipid peroxidation levels in both the liver and skin with ginseng root extract treatment, as compared to carcinogen-treated control group. Conclusion: These results suggest that P. ginseng has the potential to become a pivotal chemopreventive agent that can reduce cancer in mammals.