• Title/Summary/Keyword: chemoprevention effect

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AN EXPERIMENTAL STUDY ON THE CHEMOPREVENTIVE EFFECT OF CHLOROPHYLLIN IN HAMSTER CHEEK POUCH TUMOR INDUCED BY 7, 12-DIMETHYLBENZ[A]ANTHRACENE (7, 12-dimethylbenz[a]anthracene(DMBA)로 유발된 햄스터 협낭암에서 chlorophylln의 암예방효과에 관한 실험적 연구)

  • Yoon, Kyu-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.2
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    • pp.137-145
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    • 2000
  • Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and $3.7{\pm}0.6$ to $1.4{\pm}0.3$, respectively. The occurrence of histidine revertant by $20{\mu}mole$ DMBA was inhibited 25.6 to 81.7% by 1 to $5{\mu}M$ CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

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Inhibitory Effect of Capsaicin against Carcinogen-induced Oxidative Damage in Rats

  • Yu, Ri-Na;Park, Min-Ah;Kawada, Teruo;Kim, Byung-Sam;Han, In-Seob;Yoo, Hoon
    • Preventive Nutrition and Food Science
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    • v.7 no.1
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    • pp.67-71
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    • 2002
  • Capsaicin (trans-8-methyl-N-vanillyl-6-nonenarnide), a major pungent component of hot pepper, is known to exert antioxidative properties. In this study, we investigated the protective effects of capsaicin against chemical carcinogen-induced oxidative damage in rats. Male Sprague Dawley rats weighting 230~250 g were treated with chemical carcinogens such as 2-nitropropane (2NP) or n-methyl-N'-nitro-N-nitrosoguanidine (MNNG) after (or before) the administration of capsaicin at doses of 0.5, 1,5 mg/kg. The level of lipid peroxidation in rat liver was estimated by measuring the amounts of thiobarbituric acid reactive substances. The degree of oxidative DNA damage was evacuated by measuring a DNA adduct, 8-hydroxydeoxyguanosine (8-OHdG), in urine. Antioxidative activities of capsaicin and its metabolites in vitro were determined by the measurement of DPPH (1,1-diphenyl-2-picrylhydrazyl), a radical quencher. Significant inhibition of 2-NP induced lipid peroxidation was observed in the liver of the rat when treated with capsaicin. MNNG-induced urinary excretion of 8-OHdG was decreased by capsaicin treatment. Capsaicin and its metabolites inhibited net only the formation of free radicals, but also lipid peroxidation in vitro. Our results show that capsaicin may function as a free radical scavenger against chemical carcinogen-induced oxidative cellular damage in vivo. The observed antioxidative activities of capsaicin may play an important role in the process of chemoprevention.

Effect of Deep Sea Water on Cytochrome P450 1A1, Aromatase and MMP-9. (해양심층수의 cytochrome P450 1A1, aromatase 및 MMP-9 활성 억제 효과)

  • Shon, Yun-Hee;Kim, Mee-Kyung;Nam, Kyung-Soo
    • Journal of Life Science
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    • v.18 no.4
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    • pp.503-508
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    • 2008
  • Deep sea water from the East sea was tested for breast cancer chemoprevention and metastasis by measuring the activities of cytochrome P450 1A1 and aromatase, invasiveness, and activity and expression of matrix metalloproteinase (MMP)-9 in breast MDA-MB-231 cancer cell. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity. Deep sea water showed 27.1, 45.4 and 51.9% inhibition of microsomal aromatase activity at the hardness of 600, 800 and 1,000, respectively. In addition deep sea water inhibited not only the invasiveness of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MDA-MB-231 cells through matrigel-coated membrane in a hardness-dependent manner but also the activity and expression of MMP-9 in MDA-MB-231 cell.

Chemopreventive Potential of Coumarin in 7,12-dimethylbenz[a] anthracene Induced Hamster Buccal Pouch Carcinogenesis

  • Baskaran, Nagarethinam;Manoharan, Shanmugam;Karthikeyan, Sekar;Prabhakar, Murugaraj Manoj
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5273-5279
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    • 2012
  • The aim of the present study was to investigate the chemopreventive effect of coumarin against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis by monitoring tumor incidence and histopathological changes as well as by analyzing the status of biochemical markers (lipid peroxidation, enzymatic and non-enzymatic antioxidants, phase I and phase II detoxification enzymes). Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We noted 100% tumor formation with marked abnormalities in the biomarkers status in hamsters treated with DMBA alone. Oral administration of coumarin at a dose of 100 mg/kg body weight (bw) to DMBA treated hamsters completely prevented the tumor formation as well as restored the staus of biochemical variables. The results of the present study thus suggest that the chemopreventive effect of coumarin is probably due to its anti-lipid peroxidative potential and modulating effect on carcinogen detoxification agents in favor of the excretion of ultimate carcinogenic metabolites of DMBA during DMBA-induced hamster buccal pouch carcinogenesis.

Effect of Genistein on Chemopreventive Activity of Human Brest Cancer (Genistein이 유방암예방 활성에 미치는 영향)

  • Shon Yun-Hee;Kim Ho-Chang;Nam Kyung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.88-92
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    • 2006
  • Genistein was tested for chemopreventive potential against breast cancer by measuring the effect on proliferation of human breast cancer cells, human placental aromatase activity and cyclooxygenases-2 (COX-2) expression and activity, Genistein inhibited the growth of estrogen-independent MDA-MB-231 human breast cancer cell. However, there is no inhibitory effect of genistein on human placental aromatase activity. The expression of COX-2 was inhibited by genistein in Western blot analysis. Genistein significantly inhibited COX-2 activity at the concentrations of 10 (p<0.05), 25 (p<0.05) and 50 ${\mu}M$ (p<0.01). These results suggest that genistein may have breast cancer chemopreventive potential by inhibiting the growth of human breast cancer cell and expression and activity of COX-2.

Effect of Thesium Chinese Turczaninow Aqua-acupuncture Solution and Astragail Radix Aqua-acupuncture Solution on Promotion/ progression of Carcinogenesis (하고초와 황기 약침액이 발암 진행과정에 미치는 영향)

  • 손윤희;박신화;류준선;조경희;임종국;남경수
    • Journal of Life Science
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    • v.11 no.4
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    • pp.335-339
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    • 2001
  • Cancer chemoprevention refers to the use of natural or synthetic substances to prevent initiational and promotional events that occur during the process of carcinogenesis. Thesium Chinese Turczaninow aqua-acupuncture solution (TCTAS) and Astragli Radix aqua-acupuncture solution (ARAS) were tested as the cancer chemopreventive agents using biochemical markers of carcinogenesis. The effects on the inhibition of phorbol 12- myristate 13-acetate(TPA)-induced free radical formation in HL-60 cells and the inhibition of polyamine metabolism were measured. There is significant inhibition of TAP-induced free radical formation in human leukemic cells with cells with ARAS. Proliferation of Acanthamoeba castellanii was inhibited by TCTAS and ARAS. TCTAS and ARAS positive in these assays may inhibit the carcinogenesis process and is considered promising cancer-preventing agents.

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Effect of Water Extracts from Thesium chinense Tunczaninov and Prunella vulgaris L. on Aromatase and Cyclooxygenase Activities (하고초 열수추출물이 Aromatase와 Cyclooxygenase 활성에 미치는 영향)

  • Nam, Kyung-Soo;Shon, Yun-Hee
    • Korean Journal of Pharmacognosy
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    • v.35 no.2 s.137
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    • pp.147-151
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    • 2004
  • Water extracts from Thesium chinense Tunczaninov (TCTW) and Prunella vulgaris L. (PVW) were tested for aromatase and cyclooxygenase activities. TCTW and PVW were capable of suppressing aromatase in a human placenta microsomal assay. PVW was shown to be more effective than TCTW in the suppression of aromatase activity. TCTW significantly inhibited cyclooxygenase-2 (COX-2) activity at the concentration of 0.25 (p<0.05), 0.5 (p<0.01) and 2.5 mg/ml (p<0.005). PVW also inhibited COX-2 activity in a dose-dependent manner in a concentration range of $0.05{\sim}2.5\;mg/ml$. The expression of COX-2 was inhibitied by TCTW and PVW in western blot analysis. These results suggest that TCTW and PVW may have breast cancer chemopreventive potentials by inhibiting aromatase and cyclooxygenase activities.

MECHANISM OF CHEMOPREVENTION OF CARCINOGENIC HETEROCYCLIC AMINES BY TEA POLYPHENOLS AND COFFEE LIPIDS

  • Fred F. Kadlubar;Lin, Dong-xin;Daniel A. Casciano
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.41-42
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    • 2001
  • The chemopreventive effect of tea against 2-amino-l-methyl-6-phenylimidazo[4, 5-b ]pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% w/v) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body wt) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the $^{32}$ P-postlabelling technique.(omitted)

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CHEMOPREVENTION AGAINST DIETARY MUTAGENS IN HUMANS BY INGESTION OF CRUCIFEROUS VEGETABLES

  • Steinkellner, Hans;Gsur, Andrea;Kundi, Michael;Knasmuller, Siegfried
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.83-84
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    • 2001
  • Results from laboratory experiments indicate that induction of phase II enzymes by dietary constituents leads to inactivation of genotoxins. In animal studies glutathione S-transferase (GST) induction was paralleled by a reduction of chemically induced tumours. However data on induction of phase II enzymes in humans is scarce. Therefore we carried out intervention studies in which we investigated the effect of cruciferous vegetables on GST induction, and studied the effects of these vegetables on meat derived urinary mutagenicity.(omitted)

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Activating Transcription Factor 3 is a Molecular Target for Apoptotic Effect of Silymarin in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.29 no.3
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    • pp.281-288
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    • 2016
  • Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.