• Journal of Life Science
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• v.27 no.8
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• pp.965-973
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• 2017

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid with conjugated double bonds at C9,C11 and C10,C12 positions. Of possible CLA isomers, a naturally occurring CLA isomer is c9,t11-CLA which is produced from linoleic acid by linoleate isomerase from various rumen and lactic bacteria, and mushroom mycelia. Meanwhile, synthetically prepared CLA contained an equal amount of c9,t11-CLA and t10,c12-CLA isomers, and other isomers as minor constituents. CLA was firstly mentioned in 1939 during the elaidinization reaction of linoleic acid. Thereafter, CLA was not an attractant to scientists because it was not scientifically interested any more. However, since the anticarcinogenic action was driven from 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis in 1987, CLA-related researches were drastically elevated, resulting in approximately 6,100 research papers in literature, so far. CLA exhibited the significant biological activities: anticarcinogenic, antidiabetic, antihypertensive, antiatherosclerotic, body-fat reducing, antioxidative, antiinflammatory, testosterone producing and other activities. Interestingly, two major CLA isomers, c9,t11-CLA and t10,c12-CLA, exhibited different biological activities. Meanwhile, t,t-CLA isomers which is minor constituent of chemically synthesized CLA from linoleic acid exhibited more potent anticarcinogenic activity in carcinogen-induced animal models and cancer cell lines than other CLA isomrs. In the present review, the significant biological activities of CLA were discussed along with historical studies of CLA since 1939.

• Archives of Pharmacal Research
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• v.26 no.8
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• pp.585-590
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• 2003

Activity-guided fractionation of the EtOAc-soluble extract of the whole plants of Sida acuta using a bioassay based on the induction of quinone reductase (OR) in cultured Hepa 1c1c7 mouse hepatoma cells, led to the isolation of ten active compounds of previously known structure, quindolinone (1), cryptolepinone (2), 11-methoxyquindoline (3), N-trans-feruloyltyramine (4), vomifoliol (5), loliolide (6), 4-ketopinoresinol (7), scopoletin (8), evofolin-A (9), and evofolin-B (10), along with five inactive compounds of known structure, ferulic acid, sinapic acid, syringic acid, ($\pm$)-syringaresinol, and vanillic acid. These isolates were identified by physical and spectral data measurement. A new derivative of quindolinone, 5,10-dimethylquindolin-11-one (1a) was synthesized and characterized spectroscopically. Of the active substances, compounds 1-3 and 1a exhibited the most potent QR activity, with observed CD (concentration required to double induction) values ranging from 0.01 to 0.12 $\mu$ g/mL. Six compounds were then evaluated in a mouse mammary organ culture assay, with cryptolepinone (2), N-trans-feruloyltyramine (4), and 5,10-dimethylquindolin-11-one (1a) found to exhibit 83.3, 75.0, and 66.7% inhibition of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions, respectively, at a dose of 10 $\mu\textrm{g}$/mL.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2533-2539
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• 2012

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.263-269
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• 1998

It is an established fact that most of the carcinogens implicate bay-region diol epoxides as the ultimate carcinogenic metabolites. These electrophiles react with nucleophilic sites in the cells to form abducts. It is the formation of carcinogenic-DNA adducts that is thought to initiate carcinogenesis. In our previous study we have reported chemopreventive property of Ginseng on 7,12-dimethylbenz (a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. In this study we have examined the effect on formation of DMBA-DNA adducts in rat hepatocytes pretreated with ginseng. Primary cultures of rat hepatocytes were used. The cells wets treated with ginseng for 24 hrs and then with DMBA (iOn) for 18 hrs. Cells were then harvested, their DNA was isolated and analyzed by P)2 labelling. A significant reduction in the levels of DMBA-DNA adduces (adducts/108 nucleotides) was observed in all cultures pretreated with ginseng. The viability of cells was not affected by pre-treatment with ginseng. Our finding suggests that ginseng block or suppresses the events associated with chemical carcinogenesis by inhibiting metabolic activation of the carcinogens.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2001.10a
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• pp.71-73
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• 2001

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.85-86
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• 2001

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3343-3347
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• 2012

The aim of this study was to investigate the anticlastogenicity as well as the clastogenicity of Eryngium foetidum leaf (EF) using the in vivo mouse peripheral blood erythrocyte micronucleus assay. Eighty ICR male mice were fed AIN-76 diet supplemented with ground freeze-dried EF at 0.0%, 0.8%, 1.6% and 3.2% for 2 weeks prior to the administration of both direct-acting, mitomycin C (MMC), and indirect-acting, 7, 12-dimethylbenz(a) anthracene (DMBA) clastogens. Peripheral blood samples were collected from mice just before administration of clastogen and at 24 and 48 h thereafter for MMC. Blood samples were collected at the same times and after 72 h for DMBA. Then, reticulocytes in blood samples were counted using fluorescent microscopy. The results indicated that EF had no clastogenic effect in mice. All doses of diets supplemented with EF decreased the number of micronucleated peripheral reticulocytes in all the MMC-treated groups in a dose dependent manner, but significant reduction was found only at 1.6% and 3.2% EF in the DMBA-treated groups. It can be concluded that EF has no clastogenicity, but possesses anticlastogenic potential against both direct- and indirect-acting types of clastogen in mice.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.312-318
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• 2002

Dioxin represents a group of halogenated aromatic hydrocarbons of which 2,3,7,8-tetrachlorod-ibenzo-p-dioxin (TCDD) is well known for its extremely toxic properties as well as ubiquitous presence in our environment and ecosystems. In order to better assess the carcinogenic mechanism of dioxin, we should utilize the reliable biomarkers that can precisely and correctly reflect multi-stage carcinogenesis. When MCF10A cells were exposed to TCDD (10 nM), expression of both CYP1A1 and CYP1B1 was induced in a time-related manner. The expression as well as activity of ornithine decarboxylase was transiently induced by TCDD treatment. In contrast, the induction of COX-2 that is implicated in carcinogenesis as well as inflammation, was not induced by TCDD. In another study, gap-junctional intercellular communication (GJIC) was attenuated by TCDD treatment as revealed by the dye-transfer assay. Based on these findings, TCDD has both tumor initiating and promoting potential in human breast epithelial cells in culture. Also, treatment of MCF10A cells with the carcinogen 7,12-dimethylbenz[a]anthracene plus TCDD resulted in malignant cell transformation as revealed by increased anchorage-independent growth of exposed cells. Additional studies may be necessary to assess the effects of TCDD on multi-stage carcinogenesis in vivo.

• 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 Korean Society of Toxicology Conference
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• 2001.05a
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• pp.145-145
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• 2001

Xanthorrhizol is a sesquiterpenoid isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) that has been traditionally used in Indonesia for dietary and medicinal purposes. In our studies to evaluate the cancer chemopreventive potential, xanthorrhizol inhibited the mutagenesis induced by reactive oxygen species in Sa;monella typhimurium TA 102 in a dose-related manner and decreased significantly the incidence and the multiplicity of skin tumors initiated by 7, 12-dimethylbenz[$\alpha$]anthracene and promoted by 12-Ο-tetradecanoylphorbol-13-acetate at 19 weeks.(omitted)