• 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.

• Journal of Nutrition and Health
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• v.55 no.1
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• pp.47-58
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• 2022

Purpose: Obesity and a high-fat diet (HFD) are risk factors for colorectal cancer. We have previously shown that luteolin (LUT) supplementation in HFD-fed mice markedly inhibits tumor development in chemically induced colon carcinogenesis. In this study, we evaluated the anticancer effect of LUT in the inhibition of cell proliferation in HFD-fed obese mice and HT-29 human colorectal adenocarcinoma cells grown in an adipocyte-derived medium. Methods: C57BL/6 mice were fed a normal diet (ND, 11.69% fat out of total calories consumed, n = 10), HFD (40% fat out of total calories consumed, n = 10), HFD with 0.0025% LUT (n = 10), and HFD with 0.005% LUT (n = 10) and were subjected to azoxymethane-dextran sulfate sodium chemical colon carcinogenesis. All mice were fed the experimental diet for 11 weeks. 3T3-L1 preadipocytes and HT-29 cells were treated with various doses of LUT in an adipocyte-conditioned medium (Ad-CM). Results: The weekly body weight changes in the LUT groups were similar to those in the HFD group; however, the survival rates of the LUT group were higher than those of the HFD group. Impaired crypt integrity of the colonic mucosa in the HFD group was observed to be restored in the LUT group. The colonic expression of proliferating cell nuclear antigen and insulin-like growth factor 1 (IGF-1) receptors were suppressed by the LUT supplementation in the HFD-fed mice. The LUT treatment (10, 20, and 40 µM) inhibited the proliferation and migration of HT-29 cells cultured in Ad-CM in a dose-dependent manner, as well as the differentiation of 3T3-L1 preadipocytes. Conclusion: These results suggest that the anticancer effect of LUT is probably due to the inhibition of IGF-1 signaling and adipogenesis-related cell proliferation in colon cancer cells.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.71-76
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• 1993

It has been reported that d-limonene inhibits chemical-induced rat mammary cancer by the mechanism of increases in detoxification enzymes such as glutathione S-transferases and that cineole fails to exhibit significant suppressive effect on chemical-induced carcinogenesis. The present study was designed to compare the effects of d-limonene and cineole on the benzo(a)pyrene (BP)-induced mutagenicity, BP metabolism and lipid peroxidation. Modified Ames assay was employed to evaluate the inhibitory effect of d-limonene and cineole on the BP-induced mutagenicity. The number of revertant-bearing wells was decreased by 44~77% in the presence of both BP and d-limonene compared with that of BP alone whereas cineole decreased the number of revertant-bearing wells by 28~45% at the concentrations between $2{\mu}m$m.TEX> and 2 mM. d-Limonene suppressed BP metabolism by 16, 54 and 67% at 1, 10 and 100 mM, respectively while cineole inhibited the metabolism by 16, 26 and 55% at the same concentrations. The $EC_{50}$ values for d-limonene and cineole in inhibiting lipid peroxidation were 2.0 mM and 16 mM respectively, as assayed by thiobarbituric acid method. The present study showed that d-limonene and cineole have common antimutagenic effects although d-limonone appeared to be more effective than cineole in suppressing mutation and lipid peroxidation. The results suggest that the antimutagenic effects of d-limonene and cineole may be associated with alternation in enzyme activities and with inhibition of lipid peroxidation.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.275-279
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• 1997

Helicobacter pylori (H. pylorl) infection is now established as the major pathogenic factor in chronic gastritis and peptic ulcer disease. in addition, there is accumulating evidence that H. pylori plays an important role in the process of gastric carcinogenesis. On the other hand, oriental traditional medicines have been used for stomach disease for thousands of years. In the present study, methanol extract from the stem bark of Magnolia sieboldii (M. sieboldii) and its components were investigated on their inhibitory effects against urease activity and growth of H. pylori in vitro. The methanol extract of M. sieboldii significantly inhibited the growth of H. pylori ATCC 43504 at 5 mg/ml. From the further fractionation, the chloroform fraction inhibited the bacterial growth dose-dependently. Among four fractions separated from the chloroform fraction by silica gel column chromatography, MS-C-2 was the most potent. Costunolide was isolated from the MS-C-2 subtraction by preparative TLC and recrystallization using n-hexane. Anti-H. pylori effect of costunolide was investigated using one commercial strain (H. pylori ATCC 43504) and three clinical strains (H. pylon 4, 43, 82548). Costunolide exhibited potent anti-H. pylori activity, and the MIC was around $100-200{\mu}g/ml$. However, costunolide had no inhibitory effect of H. pylori urease activity at the concentration used for the growth inhibition assay. From these results, we conclude that costunolide inhibits the, growth of H. pylori by the independent manner of H. pylori urease inhibition.

• Natural Product Sciences
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• v.2 no.2
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• pp.123-129
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• 1996

Chemical carcinogenesis is associated with the increase of intracellular polyamine levels, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse epidermal ODC activity are essential to skin tumor promotion by TPA. Therefore, for the discovery of new cancer chemopreventive agents, we have evaluated about 73 kinds of natural products to study inhibitory effects against ODC activity induced by TPA in T24 cell culture system. The total methanol extracts of plants fractionated into three layers (hexane, ethyl acetate and water layer) were tested and the hexane fraction of Angelica gigas $(root\;bark,\;IC_{50}:\;7.4\;{\mu}g/ml)$ and the ethyl acetate fraction of Corydalis ternata $(root,\;IC_{50}:\;7.5\;{\mu}g/ml)$ were the most effective on the inhibition of TPA-induced ODC activity, These active fractions are under investigation with further sequential fractionation using column chromatography.

• Toxicological Research
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• v.5 no.2
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• pp.135-149
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• 1989

The effect of Ganoderma lucidum (Polyporaceae) extract on initiation and promotion of liver preneoplastic lesions in chemical carcinogenesis were examined in male rats. Male Fisher 344 rats, 8 weeks old, were injected i.p. with diethylnitro-samine(DENA` 200 mg/kg) as an initiator and were fed on diet containing 0.02%-acetaminofluorene (2-AAF) as a promoter for 2 weeks (group 1, 2` 2-4 week) and were fed on basal diet (group 3 and 4). The rats in test groups(group 1 and 3) were fed on diet containing 0.1% of Ganoderma lucidum extract for 6 weeks (2-8 week).

• Toxicological Research
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• v.21 no.2
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• pp.99-105
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• 2005

Photo-mutagenic compounds have been known to alter skin cancer rates by acting as initiators or by affecting subsequent steps in carcinogenesis. The objectives of this study are to investigate the utility of photo-chromosomal aberration (photo-CA) assay for detecting photo-clastogens, and to evaluate its ability to predict rodent photocarcinogenicity. Photo-CA assay was performed with five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-Methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an alpha-adrenergic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and Retinoic acid (a retinoid compound closely related to vitamin A). For the best discrimination between the test substance-mediated genotoxicity and the undesirable genotoxicity caused by direct DNA absorption, a UV dose-response of the cells in the absence of the test substances was firstly analyzed. All 5 test substances showed a positive outcome in photo-CA assay, indicating that the photo-CA test is very sensitive to the photo-genotoxic effect of UV irradiation. With this limited data-set, an investigation into the predictive value of this photo-CA test for determining the photo-carcinogenicity showed that photo-CA assay has the high ability of a test to predict carcinogenicity. Therefore, the photo-CA test using mammalian cells seems to be a sensitive method to evaluate the photo-carcinogenic potential of new compounds.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2013-2018
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• 2014

The adsorption and decomposition of trimethylene oxide ($C_3H_6O$) molecule on the Al(111) surface were investigated by the generalized gradient approximation (GGA) of density functional theory (DFT). The calculations employed a supercell ($6{\times}6{\times}3$) slab model and three-dimensional periodic boundary conditions. The strong attractive forces between $C_3H_6O$ molecule and Al atoms induce the C-O bond breaking of the ring $C_3H_6O$ molecule. Subsequently, the dissociated radical fragments of $C_3H_6O$ molecule oxidize the Al surface. The largest adsorption energy is about -260.0 kJ/mol in V3, V4 and P2, resulting a ring break at the C-O bond. We also investigated the decomposition mechanism of $C_3H_6O$ molecules on the Al(111) surface. The activation energies ($E_a$) for the dissociations V3, V4 and P2 are 133.3, 166.8 and 174.0 kJ/mol, respectively. The hcp site is the most reactive position for $C_3H_6O$ decomposing.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.117-129
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• 2000

This study was carried out to examine proliferative activity and expression of c-myc oncoprotein and p2lras in normal and preneoplastic rat livers induced by an in vivo mid-term chemical carcinogenesis assay. Sixty, six-week-old male specific pathogen free Sprague-Dawley male rats were randomly divided into five groups. Group I was received a single intraperitoneal(IP) dose(200mg/kg) of diethylnitrosamine(DEN). Group 2(10 rats) was operated partial hepatectomy(PH) and Group 3 was received IP(200mg/kg) DEN, fed two weeks later with 500ppm of phenobarbital(PB). Group 4 was received IP(200mg/kg) DEN, fed two weeks later 500ppm(PB) and PH at week 3 after the onset of experiment. While group 5(20 rats) was not treated and used as a control group. All the rats were sacrificed at age 14 weeks except 10 rats from group 5 were sacrificed at the onset of experiment. Livers of all rats were examined for 5-bromo-2'-deoxyuridine(BrdU) incoporation, proliferating cell nuclear antigen(PCNA), silver-binding nucleolar organizer regions(AgNORs) counts per nucleus and expression of c-myc oncoprotein and p21ras. Both the number and area of the preneoplastic lesions were significantly(p<0.01) compared to other groups. A significant(p<0.01) increase in immunoreactive cells were detected in preneoplastic hepatocytes in Groups 3 and 4 by PCNA and BrdU immunohistochemical stain. The number of the positive cells were significantly(p<0.05) lower in normal 14-week-old rats than those of 6-week-old rats. The results showed that proliferative activity of the hepatocytes was increased by treatment with DEN, PH and PB. Meanwhile, AgNORs counts per nucleus were significantly(p<0.05) increased in the preneoplastic hepatocytes of rats in both groups 3 and 4. The expression of c-myc oncoprotein and p21ras were more readily localized within the hepatic preneoplastic lesions such as hyperplastic nodules. Especially, group 4 showed significantly (p<0.05) overexpressed levels compared to groups 1 and 3. These findings suggest that PCNA, BrdU and AgNORs are significantly increased and c-myc oncoprotein and p21ras are significantly overexpressed in hepatic preneoplastic lesions induced by mid-term carcinogenesis. So these parameters can be an effective markers for hepatic prencoplastic lesions.

• Journal of Nutrition and Health
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• v.51 no.1
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• pp.14-22
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• 2018

Purpose: Colorectal cancer, which is one of the most commonly diagnosed cancers in developing and developed countries, is highly associated with obesity. The association is largely attributed to changes to western style diets in those countries containing high-fat and high-energy. Luteolin (LUT) is a known potent inhibitor of inflammation, obesity, and cancer. In this study, we investigated the effects of LUT on chemical-induced colon carcinogenesis in high fat diet (HFD)-fed obese mice. Methods: Five-week-old male C57BL/6 mice received a single intraperitoneal injection of azoxymethane (AOM) at a dose of 12.5 mg/kg body weight. Mice were then divided into four groups (n = 10) that received one of the following diets for 11 weeks after the AOM injection: normal diet (ND); HFD; HFD with 0.0025% LUT (HFD LL); HFD with 0.005% LUT (HFD HL). One week after AOM injection, animals received 1~2% dextran sodium sulfate in their drinking water over three cycles consisting of five consecutive days each that were separated by 16 days. Results: Body weight, ratio of colon weight/length, and tumor multiplicity increased significantly in the HFD group compared to the ND group. Luteolin supplementation of the HFD significantly reduced the ratio of colon weight/length and colon tumors, but not body weight. The levels of plasma $TNF-{\alpha}$ and colonic expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein increased in response to HFD, but were suppressed by LUT supplementation. Immunohistochemistry analysis also showed that iNOS expression was decreased by LUT. Conclusion: Consumption of LUT may reduce the risk of obesity-associated colorectal cancer by suppression of colonic inflammation.