• Journal of Life Science
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• v.14 no.1
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• pp.154-162
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• 2004

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated and at transcriptional level by external stimuli. Previously, we found that phorbol 12-myristate 13-acetate (PMA) suppressed TSP-1 expression in porcine aortic endothelial (PAE) cell, but enhanced in hepatoma cell line, Hep 3B cell. A region between -767 and -723 on the tsp-1 promoter was defined as a responsive site to the suppression in PAE cell. eased on the previous results, the molecular mechanism of TSP-1 expression was determined by characterizing interactions between cis-elements and trans-factors using three overlapped oligonucleotide probes, oligo a-1 (from -767 to -738), a-2 (-759 to -730) and a-3 (-752 to -723). The results from electromobility shift assay showed that PMA-induced suppression of TSP-1 transcription in PAE cell might be caused via a negative regulator binding to the region from -752 to -730 and additionally generated by lacking two positive regulators binding to the sites from -767 to -760 and from -752 to -730. Especially, PMA enhanced the binding ability of the negative regulator to the site from -752 to -730 in PAE cell, but anti-c-Jun did not affected its binding ability.

• Korean Journal of Acupuncture
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• v.18 no.1
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• pp.11-20
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• 2001

Cancer chemoprevention refer to the use of natural or synthetic substances to prevent the initiational and promtional events that occur during the process of carcinogenesis. The effect of Prunella Herba Vulgaris L. Aqua-acupuncture Solution (PVAS) and Prunella Herba Vulgaris L. Water-extracted Solution (PVWS) on the induction of phase II detoxification enzyme (quinone reductase, Glutathione S-transferase) and inhibition of phase I enzyme (cytochrome P4501A1) and benzo[a]pyrene-DNA adduct formation was examined. PVAS is potent inducers of quinone reductase activity. Glutathione levels were increased with PVAS, in cultured murine hepatoma Hepa1c1c7 cells. In addition glutathione S-transferase levels were increased with PVAS. However, there was 45.2% inhibition in the activity of cytochrome P4501A1 enzyme with the treatment of PVAS, $5{\times}$. At concentration of $1{\times}$ and $3{\times}$ of PVAS, the binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cell was inhibited by 25.3%, 45.0%, respectively. These results suggest that PVAS has chemopreventive potential by inducing quinone reductase and glutathione S-transferase activities, increasing GSH levels, inhibiting the activity of cytochrome P4501A1 and benzo[a]pyrene-DNA adduct formation.

• Journal of Life Science
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• v.18 no.3
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• pp.381-386
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• 2008

Deep sea water was tested for cancer chemopreventive activity by measuring the activities of ${\beta}-$ naphthoflavone $({\beta}-NF)-induced$ cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. 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 CYP 1A2 activity. QR and GST activities were induced about $1.1{\sim}1.2$ fold with the treatment of deep sea water in murine hepatoma Hepa 1clc7 cells. In addition GSH levels were increased $1.3{\sim}1.4$ fold in a hardness range of $100{\sim}1,000$. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-a-cetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

• 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.

• Korean Journal of Food Science and Technology
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• v.41 no.5
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• pp.552-559
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• 2009

In this study, the anticancer activity of the water extract at $100^{\circ}C$ was compared to that of the callus extracts via a ultrasonification extraction process. All the extracts were utilized to evaluate cytotoxicity, antioxidant and immune activities. The callus extracted via ultrasonification extraction showed relatively low cytotoxicity on normal human cell lines, HEK293 and HEL299, showing 13.17% and 21.78%, respectively. The callus extract has 59.82% which was similar to 61.70% for water extracts. It was also found that callus extract yielded higher nitric oxide secretion form macrophage than other extracts. The growths of both human stomach adenocarcinoma (AGS) cell and human lung carcinoma (A549) were inhibited up to 70% by adding 1.0 mg/mL of the callus extracts with ultrasonification extraction. This inhibition ratio (70%) was almost close to that of water extract. Human hepatoma carcinoma (HEP3B) cell growth was most significantly inhibited up to 75% by adding 1.0 mg/mL of callus extracts, and its selectivity was highest compared to other extracts. It indicates that the callus extracts could selectively inhibit growth of digestive system-related cancer cells. It can be also concluded from the results of this study that the callus extracts associated with ultrasonification extraction process have the potential for anticancer activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.573-580
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• 2005

Cholesterol $7\alpha-hydroxylase$ (CYP7A1) is the rate-limiting enzyme in the conversion of cholesterol to bile acids and plays a central role in regulating cholesterol homeostasis. We previously showed that a fermentable $\beta-glucan$ ingestion decreased plasma cholesterol levels due to fecal bile acid excretion elevation involved inincrease of cholesterol $7\alpha-hydroxylase$ mRNA expression and activity. It is proposed that short chain fatty acids (SCFA) produced by cecal and colonic fermentation of soluble fiber are associated with cholesterol-lowering effect of fiber. In the present study, we investigated whether CYP7A1 expression is up-regulated by short chain fatty acids or by hormones in cultured human hepatoma (HepG2) cells. Confluent HepG2 cell were incubated with acetate, propionate, or butyrate at 1 mM concentration for 24 hrs. Acetate as well as propionate increased to 1.8-fold expression of CYP7A1 mRNA than the control. Butyrate also increased 1.5-fold expression of CYP7A1 mRNA. Our data show for the first time that SCFA increase expression of CYP7A1 mRNA. Adding insulin, dexamethasone and triiodothyronine $(1\;{\mu}M)$ to HepG2 cell increased the expression of CYP7A1 mRNA to $150\%,\;173\%,\;141\%$, respectively. These results suggest that SCFA produced by cecal fermentation stimulate enteric nervous system, in which secreted some neuropeptides may be responsible for change in cholesterol and bile acid metabolism. These findings suggest that SCFA are involved in lowering plasma cholesterol levels due to the up-regulation of CYP7A1 and bile acid synthesis.