• Korean Journal of Pharmacognosy
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• v.34 no.2 s.133
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• pp.161-165
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• 2003

Ethanol extract from Thesium chinense Tunczaninov (TCTE) was tested for breast cancer chemopreventive activity by measuring 7,12-dimethylbenz[a]anthracene (DMBA) - induced cytochrome P450 1A1 activity, induction of quinone reductase and glutathione S-transferase, and glutathione level. TCTE significantly inhibited cytochrome P45O 1A1 activity at the concentration of 90 and 150 mg/ml. TCTE induced quinone reductase activity in a dose-dependent manner in a concentration range of 3-150 mg/ml. In addition glutathione S-transferase activity and glutathione level were increased with TCTE in cultured murine hepatoma Hepa1c1c7 cells. These results suggest that TCTE has breast cancer chemopreventive potential by inhibiting cytochrome P45O 1A1 activity, inducing quinone reductase and glutathione S-transferase activities, and increasing GSH level.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.270-280
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• 1998

Ginseng is one of the most widely used medicinal plants, particularly in East Asian countries. Certain fractions or purified ingredients of ginseng have been shown to exert inhibitory effects on growth of cancer cells in culture or on tumorigenesis in experimental animals. Moreover, a recent epidemiologic study reveals that ginseng intake is associated with a reduced risk for environmentally related cancers such as esophageal, gastric, colorectal, and pulmonary tumors. Heat treatment of Panax ginseng C. A. Meyer at the temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed ginseng (designated as'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in f Xl 74 supercoiled DNA Induced by UV photolysis of H2O2 and was also capable of scavenging superoxide generated in vitro by xanthine/xanthine oxidate or in differentiated human promyelocytic leukemia (HL-60) cells by the tumor promoter,12-0-tetvade- canoylphorbol-13-acetate (TPA). Since tumor promotion is closely linked to oxidative stress, we have determined possible anti-tumor promotional effects of NGMe on two-stage mouse skin tumorigenesis. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA significantly ameliorated skin papillomagenesi s initiated by 7,12-dimethylbenz (a) anthracene (DMBA).'Likewise, TPA-induced epidermal ornithine decarboxylase activity and elevation of tumor necrosis factor-a were suppressed signifies%fly by NGMe pretreatment. NGMe topically applied onto surface of hamster buccal pouch 10 min before each topical application of DMBA inhibited oral carcinogenesis by 76olo in terms of multiplicity. Taken together, these results suggest that processed Panax ginseng C. A. Meyer has potential cancer chemopreventive activities.

• Toxicological Research
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• v.33 no.3
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• pp.211-218
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• 2017

Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates potential carcinogens. Moreover, its expression in tumor tissues is much higher than that in normal tissues. Despite this association between CYP1B1 and cancer, the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells remains unknown. Previous reports indicated that the mRNA expression level of Herc5, an E3 ligase for ISGylation, is promoted by CYP1B1 suppression using specific small interfering RNA, and that ISGylation may be involved in ubiquitination related to ${\beta}-catenin$ degradation. With this background, we investigated the relationships among CYP1B1, Herc5, and ${\beta}-catenin$. RT-PCR and western blot analyses showed that CYP1B1 overexpression induced and CYP1B1 inhibition reduced, respectively, the expression of $Wnt/{\beta}-catenin$ signaling target genes including ${\beta}-catenin$ and cyclin D1. Moreover, HeLa cells were treated with the CYP1B1 inducer $7,12-dimethylbenz[{\alpha}]anthracene$ (DMBA) or the CYP1B1 specific inhibitor, tetramethoxystilbene (TMS) and consequently DMBA increased and TMS decreased ${\beta}-catenin$ and cyclin D1 expression, respectively. To determine the correlation between CYP1B1 expression and ISGylation, the expression of ISG15, a ubiquitin-like protein, was detected following CYP1B1 regulation, which revealed that CYP1B1 may inhibit ISGylation through suppression of ISG15 expression. In addition, the mRNA and protein expression levels of Herc5 were strongly suppressed by CYP1B1. Finally, an immunoprecipitation assay revealed a direct physical interaction between Herc5 and ${\beta}-catenin$ in HeLa cells. In conclusion, these data suggest that CYP1B1 may activate $Wnt/{\beta}-catenin$ signaling through stabilization of ${\beta}-catenin$ protein from Herc5-mediated ISGylation for proteosomal degradation.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.474-478
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• 1999

Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methly methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7, 12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea $(5{\times}10^{-3} M)$was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from $(1{\times}10^{-6} M)$ to$(5{\times}10^{-4} M)$ did not significantly inhibit unscheduled DNA synthesis induced by either MMS $(1{\times}10^{-4} M)$ or EMS $(1{\times}10^{-2} M)$. In contrast, DHEA-significantly inhibited unscheduled DNA synthesis induced by BaP $(6.5{\times}10^{-5} M)$ and DMBA.$(2{\times}10^{-5} M)$. DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.

• Preventive Nutrition and Food Science
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• v.2 no.3
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• pp.241-245
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• 1997

Inhibitory effects of kimchi extracts on arcinogen-induced cytotoxicity and transformation in C3H/10T1/2 cells were studied. The methanol extract (500㎍/ml) of fresh (unfermented kimchi), and 3-week-fermented kimchi (properly ripened kimchi at 5℃) inhibited 3-methylcholanthrene (MCA)-induced cytotoxicity in C3H/10T1/2 cells by 84 and 99%, respectively. The inhibitory effect of 3-week-fermented kimchi was higher than that of the fresh kimchi at same test condition. The methanol soluble fraction, and haxane extract of 3-week fermented kimchi also surpressed the cytotoxicity of FC3H/10T1/2 cells mediated by 7,12-dimethylbenz[a]anthracene(DMBA) and N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). Furthermore, MCA-induced transformation of C3H/10T/1/2 cells was significantly inhibited by the methanol soluble fraction of 3-week fermented kimchi. With these results, we suggest that kimchi might have anticarcinogenic effect in part due to inhibition of carcinogen-induced cytotoxicity and transformation of C3H/10T/1/2 cells.

• Journal of Ginseng Research
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• v.24 no.4
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• pp.188-195
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• 2000

Using Ginseng saponins (crude saponin and total saponin) and ginsenoside Rbl Rb2, Rc, Rd, Re, Rhl, and Rh2 in this study, we have examined the effects of the compounds on the induction of differentiation in normal rat mammary epithelial cells and 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor cells in culture. When normal rat mammary organoids were cultured in 100-mm culture plates in the presence or absence of ginseng saponins, there were four different cell colonies after two weeks in culture: cobble stone, spindle, honey comb, and senescence type colonies. Ginseng saponins showed different effects on the development of each colonies. Scrape-loading dye transfer tech-nique was performed to measure the effects of total saponin, Rhl, and Rh2 on intercellular junctional communication. Intercellular communication was not observed at short cultilral time, e.g., four or seven days, but when it cultured it up to two weeks, cell to cell communication was observed in saponin-treated cells. Reconstituted basement membrane, Matrigel, supported the growth and development several different multicellular structures from normal mammary organoids (e.g., ductal, webbed, stellate, and squamous colonies) or DMBA-induced mammary tumor (e.g., alveolar unit, foamy alveolar unit, squamous metaplasia, lobule-ductal, stellate, and webbed colony). In ginseng saponin-treated groups, webbed colonies were more and squamous colonies were less than control group. Moreover, the ductal colonies, marker tructure of well-differentiate mammary epithelial cells, were developed more in saponin-treated group than in control group. In conclusion, ginseng saponins affected on the differentiation of normal rat mammary epithelial cells and DMBA-induced mammary tumor cells in culture.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.462-470
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• 2012

Mountain cultivated ginseng (MCG) is a type of Panax ginseng C. A. Mayer, grown in the mountains by artificial seeding. In general, it has been known that the biophysical activities of MCG is greater than that of ginseng. However, the in vivo efficacy of MCG on cancer has not been studied. In this study, we investigated the anti-carcinogenic effect of MCG and ginseng using the 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanoylphorbol- 13-acetate (TPA) two stage mouse skin carcinogenesis model. Six weeks of female ICR mice were divided into control, MCG, and ginseng diet groups and were subjected into two different experimental protocols. In the first study, each experimental diet was fed with TPA promotion for 24 weeks. The result showed that supplementation of MCG reduced tumor incidence, tumor multiplicity, and tumor size compared to those of the control and ginseng groups. In the second study, 3 groups of mice were supplied with each diet 4 weeks before DMBA tumor initiation, until the end of experiment. The result showed that tumor incidence, tumor multiplicity, and tumor size were reduced in the ginseng diet group compared to those of the control and MCG groups. TPA-induced BrdU incorporation was also significantly reduced in the ginseng diet group. Taken together, these results suggest that MCG is chemotherapeutic, whereas ginseng has a chemopreventative effect on mouse skin cancer.

• Journal of Nutrition and Health
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• v.31 no.5
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• pp.906-913
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• 1998

This study an analyzes the effects of the P/S ratio of dietary lipids and antioxidant vitamin supplements on serum lipids level and fatty acid profile, the degree of lipid peroxidation, and the antioxidant enzyme activities in the liver of rats treated with 7,12-dimethylbenz($\alpha$) anthracene(DMBA). P/S ratio of dietary lipids was made into 0.5, 1 and 2 by mixing palm oil, soybean oil, sesame oil and perilla oil at 10%(w/w) fat level and n-6/n-3 ratio was fixed to 4. Antioxidant vitamin of $\alpha$-tocopherol or $\beta$-carotene was supplemented in addition to vitamin mixture which was given at 1 % of the standard diet. female Sprague-Dawley strain rats, about 60 days old, were divided into three groups(LP : low P/S ratio(0.5), MP : medium P/S ratio (1.0), HP , high P/S ratio(2.0)) and each group was sub-divided into three groups(S ; standard, T ; tocopherol supplemented, C : carotene supplemented): Two weeks after feeding experimental diets, all groups were treated with a single dose of DMBA(2mg/100g BW) by gastric intubation and fed experimental diet for 9 week. The results were as follows ; 1) Serum total cholesterol(TC) level was not significantly influenced by diet but tended to be lower in HP groups compared to LP and MP groups. Triglyceride level was the highest in LP groups and the lowest in $\alpha$-tocopherol supplemented groups. 2) Thiobarbituric acid reactive substance(TBARS) level, representing lipid peroxidation in hepatic microsome, tended to be increased as the unsaturation of dietary lipids increases. $\alpha$-Tocopherol supplement significantly decreased TBARS level. 3) The activities of superoxide dismutase(SOD) and glutathione peroxidase(GSHPx) in hepatic cytosol showed the tendency to be high with increasing P/S ratio of dietary lipids. SOD activity was not significantly influenced by antioxidant vitamin, but GSHPx activity was significantly increased in $\alpha$-tocopherol supplemented groups. In summary, high polyunsaturated fat diet was effective on reducing the serum level of total cholesterol and triglyceride, while it increased unsaturation and peroxidizability of serum fatty acid. With increasing P/S ratio of dietary lipids, lipid peroxidation was increased in the liver and antioxidant enzyme system was induced to inhibit lipid peroxidation against oxidative damage. $\alpha$-Tocopherol supplement was effective in lowering lipid peoxidation, but $\beta$-carotene supplement did not exhibit antioxidant effect. (Korean J Nutrition 31(5) 906~913, 1998)

• 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.

• Preventive Nutrition and Food Science
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• v.16 no.4
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• pp.283-290
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• 2011

The recent increase of colon, breast, and prostate cancer incidence in Korea has been attributed to a diet pattern change to a more Western style, in which the foods eaten are higher in protein and fat. Whether high protein intake itself stimulates tumor cell growth and exacerbates disease status has been investigated, however, many epidemiological studies have inconsistent results between meat intake and the risk of certain cancers. These inconsistent results are partly because of the difficulty of studying the effects of just the meat intake. Other factors, such as overall meal context, could not be completely excluded in the study. To address the question of whether high protein itself is independently associated with carcinogenesis, we initiated ICR mice with 200 nmol ($50{\mu}g$) 7,12-dimethylbenz[a]anthracene (DMBA) and fed animals either a normal diet (ND, 14% casein) or a high protein diet (HPD, 50% casein) for 15 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in two-stage skin carcinogenesis protocol. There was no significant difference between ND and HPD group in food intake and body weight throughout the experiment. However, tumor multiplicity of the HPD group was decreased by 75.5% compared to that of the ND group. In addition, HPD inhibited skin hyperplasia and epidermal cell proliferation. Western analyses with whole skin lysates showed that HPD inhibited TPA-induced Akt (S473), S6K (T389), 4E-BP1 (Thr 37/46) and Erk1/2 (Thr202/Tyr204) phosphorylation as well as COX-2 expression. Taken together, these data suggest that a high protein diet has an anticarcinogenic effect by inhibiting the TPA-induced Akt signaling pathway.