• Korean Journal of Pharmacognosy
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• v.32 no.2 s.125
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• pp.163-167
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• 2001

Prunella vulgaris L. aqua-acupuncture solution (PVAS) was tested for cancer chemopreventive activity using chemoprevention-associated biochemical end points. The following effects were measured. : (a) inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P4501A1 activity (b) inhibition of $[^3H]B[a]P-DNA$ binding (c) inhibition of phorbol 12-myristate 13-acetate (TPA)-induced free radical formation in HL-60 cells (d) inhibition of polyamine metabolism. PVAS inhibited cytochrome P4501A1-mediated ethoxyresorufin-O-deethylase activity. The binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cells was inhibited significantly by PVAS. There is 22% inhibition of TPA-induced free radical formation in human leukemic cells with 5 mg/ml PVAS. Proliferation of Acanthamoeba castellanii was inhibited by PAVS at concentration of 30 mg/ml. PAVS positive in these assays may inhibit the carcinogenesis process and is considered very promising cancer-preventing agent because of its multiple activities.

• 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.

• Nutritional Sciences
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• v.5 no.2
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• pp.53-59
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• 2002

This study was conducted to examine the effects of dietary sources of fatty acids and protein on serum protein profiles, hepatic functional enzyme activities, mammary tumor incidence and tumor weight in 7, 12-dimethylbenz($\alpha$)anthracene (DMBA)-treated rats. The sources of dietary fatty acids were 18n6 (rich in linoleic acid), 18n3 (rich in linolenic acid) and 22n3 (rich in DHA) : sources of dietary protein were casein (C) and soy protein isolate (S). mammary tumors (MTs) were chemically induced by DMBA (9 mg/100 g body weight) which was gastrically intubated at 7 weeks of age. Each experimental diet was given for the following 25 weeks. Casein-fed rats (group C) exhibited significantly higher levels of weight gain and FER (food efficiency ratio) than did group S. Group C showed higher levels of serum protein and globulin, and higher albumin/globulin (A/G) ratios than group S. Liver functional enzyme activities (GOT, GPT, ALP, LDH, $\gamma$-GT) and LDH/GOT ratios were not influenced by dietary protein. GPT activity was lower in the group given 18n3, and ALP activity was lower in the group given 18n6. The incidence and total number of MTs appeared to be lower in the group given 22n3 than in the group given 18n3 or 18n6, even though the average weight of MTs was highest in the group given 22n3, The average weight of MTs was higher in the C group than in the S group. MT incidence had a positive correlation with LDH activity and LDH/GOT ratio. The average weight of MTs had a negative correlation with serum albumin levels and A/G ratios, and a positive correlation with ALP activity. This research suggests that the measurement of serum protein profiles and liver functional enzyme activities may be utilized to monitor the development of mammary tumors.

• Toxicological Research
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• v.33 no.2
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• pp.79-96
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• 2017

A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl- and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1, and 3A4 are reported to play critical roles in the bioactivation of these carcinogenic chemicals. In vivo studies have shown that disruption of Cyp1b1 and Cyp2a5 genes in mice resulted in suppression of tumor formation caused by 7,12-dimethylbenz[a]anthracene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, respectively. In addition, specific inhibitors for CYP1 and 2A enzymes are able to suppress tumor formation caused by several carcinogens in experimental animals in vivo, when these inhibitors are applied before or just after the administration of carcinogens. In this review, we describe recent progress, including our own studies done during past decade, on the nature of inhibitors of human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs and tobacco-related nitrosamines, respectively, in humans. The inhibitors considered here include a variety of carcinogenic and/or non-carcinogenic PAHs and acethylenic PAHs, many flavonoid derivatives, derivatives of naphthalene, phenanthrene, biphenyl, and pyrene and chemopreventive organoselenium compounds, such as benzyl selenocyanate and benzyl selenocyanate; o-XSC, 1,2-, 1,3-, and 1,4-phenylenebis(methylene)selenocyanate.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.27 no.2
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• pp.63-81
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• 1997

This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3123-3129
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• 2013

Background: The search for naturally occurring agents in routinely consumed foods that may inhibit cancer development is of high priority. [6]-Paradol is a pungent phenolic bioactive component from ginger with welldocumented health promoting antioxidant, antimutagenic, antigenotoxic and anti-inflammatory properties. However, anticarcinogenic effects have yet to be fully explored. The objectives of the present study were therefore to assess protective effects against 7,12-dimethylbenz(a)anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters. Methods: Oral squamous cell carcinomas developed in the left buccal pouch of hamsters on painting with 0.5% of DMBA, three times in a week. To assess the apoptotic associated gene expressing potential of [6]-paradol, it was orally administered to DMBA treated hamsters on alternate days from DMBA painting for 14 weeks. Results: We observed 100% tumor formation with marked levels of neoplastic changes and altered the expression of apoptotic associated gene (p53, bcl-2, caspase-3 and TNF-${\alpha}$) was observed in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of [6]-paradol at a dose of 30 mg/kg b.wt to DMBA treated animals on alternative days for 14 weeks significantly reduced the neoplastic changes and improved the status of apoptosis associated gene expression. Conclusion: These observations confirmed that [6]-paradol acts as a tumor suppressing agent against DMBA induced oral carcinogenesis. We also conclude that [6]-paradol also effectively enhances apoptosis- associated gene expression in DMBA treated animals.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.78-91
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• 2002

Objective : This study was designed to investigate the anti-cancer effects of bee venom on melanoma in C57BL mice. Materials and Methods : For the induction of melanoma, C57BL mice were treated by DMBA(7, 12-dimethylbenz[a]anthracene). Each group of C57BL mouse was treated with DMBA $50{\mu}g$, $75{\mu}g$, $100{\mu}g$ respectively once a week for 15 weeks. Tumor generation in each group of 10 mice was observed. Cumulative curves were showed in the density and frequency of skin tumor generation. To know the effects of pre-treatment of bee venom on tumor generation by DMBA treatment(frequency of tumor generation), Each group of C57BL mouse was pretreated and treated with bee venom $5{\mu}{\ell}$, $25{\mu}{\ell}$, $50{\mu}{\ell}$ respectively once a week for 3 weeks, whereafter each mouse was treated with DMBA $100{\mu}g$ once a week for 15 weeks. Results and Conclusion (1) There was chemotherapeutic effect, but not chemopreventive effect. (2) Cpp32 activity was increased by $50{\mu}{\ell}$ bee venom treatment. (3) Bee venom treatment inhibited expression of cell-cycle regulating, growth-promoting genes such as c-Jun, c-Fos, and Cyclin Dl, and increased tumor suppressors p53 and p21/Wafl. (4) Bee venom treatment activated expression of a representative apoptosis-inducing gene Bax.

• Food Science and Preservation
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• v.21 no.3
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• pp.301-307
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• 2014

The purpose of this study was to examine the potential of turmeric (Curcuma longa L.) to inhibit 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats. Female Sprague Dawley rats were fed a control diet (NC and DC) or an ethanol extract of turmeric (DT) diet until the end of the experiment. The rats in the DC and DT groups were administered a single dose of DMBA (50 mg/Kg) by oral gavages at 50 days of age. The turmeric ethanol extracts decreased the incidence and multiplicity of DMBA-induced mammary tumor. The turmeric ethanol extract significantly decreased the tumor cell proliferation. The turmeric also significantly decreased the tumor grade based on the degree of the tubule formation. The results suggest that the ethanol extract of turmeric has an inhibitory effect against mammary carcinogenesis, and that such chemopreventive effect may be related to the inhibition of the initiation and the proliferation of tumor cells.

• 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.

• Preventive Nutrition and Food Science
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• v.6 no.1
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• pp.57-61
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• 2001

Conjugated linoleic acid (CLA), when incorporated into mouse liver microsomal membranes, selectively inhibits the mutagenesis of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). Nine-week old female ICR mice were given (p.o.) 0.1 mL olive oil alone (control), 0.1 mL olive oil plus 0.1 mL linoleic acid, or 0.1 mL olive oil plus 0.1 mL CLA, twice weekly for four weeks. The animals were then sacrificed and liver S-9 fractions were prepared. Activation of IQ for mutagenesis by the liver S-9 from CLA-treated mice was significantly reduced in comparison wit liver S-9 from control or linolic acid-treated mice. By contrast, the activation of 7,12-dimethylbenz[a] anthracene (DMBA) and benzo[a] pyrene (BP) was unaffected. Hence, CLA incorporated into phospholipids may selectively affect cytochrome P450 isozymes responsible for activating IQ, but not those which activate BP or DMBA. The addition of free CLA or the methyl esters of CLA, linoleic acid, or oleic acid, to control S-9 inhibited the activation of all three mutagens (IQ, BP, and DMBA).