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      • SCOPUSKCI등재

        Free Radical Toxicology and Cancer Chemoprevention

        Lin, Jen-Kun The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

        Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

      • SCOPUSKCI등재

        Reversible Hepatic Toxic Effect of Crocin Dyes in Rats

        Jen-Kun Lin,Chau-Jong Wang 한국생약학회 1985 생약학회지 Vol.16 No.4

        Gardenia jasminodes has been medically used for anti-inflammation, sedation and anti-diarrhea; The extract of this plant has been traditionally used as food colorant and referred as crocin dyes. In the present study, the possible hepatic toxicity of this dye has been evaluted on the basis of its alteration on the marker enzymes, namely, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphatase, lactate dehydrogenase and gamma-glutamyltransferase. Crocin dyes did not affect hepatic function when they were orally administered to rats in a daily dose of 50 ㎎/㎏ for 8 days, but could induce acute hepatic discoloration. A high dose of 100 ㎎/㎏ for 2 weeks could induce both hepatic damage and black pigmentation, but a lower dose of 10 ㎎/㎏ for 40 days did not The induced black pigmentation and the acute hepatic damage were completely reversible. In conclusion, the crocin dyes have a very low hepatic toxicity in rats, even in high experimental dosages which could hardly happen in human practice. It is therefore suggested that the crocin dyes are safe for coloring foods.

      • SCIESCOPUSKCI등재

        Cancer Chemoprevention by Tea Polyphenols Through Modulating Signal Transduction Pathways

        Lin, Jen-Kun The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.5

        The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

      • KCI등재
      • SCIESCOPUSKCI등재

        Suppression of Protein Kinase C and Nuclear Oncogene Expression as Possible Action Mechanisms of Cancer Chemoprevention by Curcumin

        Lin, Jen-Kun The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.7

        Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

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