• Preventive Nutrition and Food Science
• /
• v.7 no.4
• /
• pp.358-366
• /
• 2002

To search for novel cancer preventive agents, we assessed the quinone reductase (QR)-inducing activities of medicinal herb extracts in cultured murine hepatoma cells (hepalclc7 cells). Among 216 herb extracts tested in this study, 8 kinds of herbal extracts were found to induce QR activity in hepalclc7 cells by more than 2-fold when used at the concentration of 25 $\mu\textrm{g}$/$m\ell$. The methanol extracts of Aster koraiensis NK and Pulsatilla koreana Nakai induced QR by 252 and 223 % , respectively, at the concentration of 25 $\mu\textrm{g}$/$m\ell$. Most of the herbal extracts with QR inducing-activity increased the enzyme activity in a typical dose-dependent manner. The QR activity in BP$^{r}$ cl cells was induced move than 50 % by the extracts of Pulsatilla koreana Nakai, Inula helenium, Physalis alkekengi var, francheti (Masters) Makino, Chrysanthemum zawadskii var. latilobum Kitamuva, Auemisia keiskeana Miquel, Chfsanthemum boreale Makino. In conclusion, hlsatilla koreana Nakai, Aster koraiensis N.K, and Chfsanthemum zawadskii var. iatilobum Kitamura, which showed relatively high QR induction, merit further animal study to evaluate their potential as cancer preventive agents.

• Journal of Veterinary Clinics
• /
• v.26 no.1
• /
• pp.29-35
• /
• 2009

This study was to determine the effects of ascorbic acid and alpha-tocopherol on the attenuation of an ischemia-reperfusion injury (IRI) after renal auto-transplantation in a pig model. In the treatment group, three pigs were subjected to a renal auto-transplantation followed by the administration of ascorbic acid and alpha-tocopherol and the flushing of ascorbic acid plus hepa-saline solution. Otherwise, the control group used only flushing of hepa-saline solution. Blood samples were collected from these pigs for measurement of serum blood urea nitrogen (BUN) and creatinine values on the day before surgery and day 1, 3, 5 and 7 after surgery. The kidneys were taken for histopathological evaluation following euthanasia on day 14 after surgery. Serum creatinine and BUN values showed a significantly difference between control and treatment group on day 1, 3 and 5 (P<0.05). In histopathologic findings, treatment group showed less damage than that of the control group on the basis of renal tubular damage. As a result, this study suggests that the exogenous ascorbic acid and alpha-tocopherol pretreatment therapy with ascorbic acid irrigation-aspiration has a role of attenuation of renal I/R injury and recovery of renal function in a pig transplantation model.

• Journal of the Korea Society of Computer and Information
• /
• v.21 no.12
• /
• pp.139-145
• /
• 2016

In this paper, we propose to evaluate the effect of Resistin-like molecule alpha (Retnla) on the expression of transporters involved in modulating concentrations of peripheral cholesterol and plasma high-density lipoprotein (HDL) cholesterol. High levels of blood cholesterol are a well-recognized risk factor for atherosclerosis and are eliminated via the process of reverse cholesterol transport (RCT). We recently showed that Retnla ameliorates hypercholesterolemia and atherosclerosis by increasing biliary cholesterol secretion, the final step of the process, in low-density lipoprotein receptor-deficient mice. However, the role of Retnla in HDL-mediated cholesterol efflux, initial step of RCT pathway, is not yet clear. To identify cholesterol transport genes regulated by Retnla, we performed an extensive microarray-based gene expression screen using livers from Retnla-overexpressing (Tg) mice and control animals. The most significant change in Retnla-Tg mice was an upregulation of ATP-binding cassette sub-family G member 4 (Abcg4) transport and was validated using quantitative RT-PCR. The validated gene was also induced by treatment of purified Retnla protein in RAW 264.7 cells incubated with acetylated low-density lipoprotein and Hepa1c1c7 cells. Taken together, these results indicates that Retnla might also accelerate initial step of RCT pathway, suggesting therapeutic value of Retnla in the treatment of hypercholesterolemia and atherosclerosis.

• Food Science and Biotechnology
• /
• v.16 no.4
• /
• pp.641-645
• /
• 2007

Delphinidin, an aglycone form of anthocyanins, was demonstrated to have anti-carcinogenic potential. The compound at $50\;{\mu}g/mL$ caused a significant increase of quinone reductase activity, an anti-carcinogenic marker enzyme, in mouse hepatoma cell lines (Hepa1c1c7 and BPRc1). Delphinidin enhanced the expression of other detoxifying or antioxidant enzymes including glutathione s-transferase, gamma-glutamylcysteine synthetase, heme oxygenase 1, and glutathione reductase. It suppressed the proliferation of murine hepatoma cells in a dose-dependent manner, with approximately $IC_{50}$ of $70\;{\mu}g/mL$. These results suggest that delphinidin might be useful for cancer prevention.

• Korean Journal of Pharmacognosy
• /
• v.31 no.1
• /
• pp.7-15
• /
• 2000

Glycyrrhizae Radix aqua-acupuncture solution (GRAS) and Glycyrrhizae Radix water-extracted solution (GRWS) were prepared and tested for organ toxicities, antitumor activities, and immunomodulatory effects. The organ-toxicity of GRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP-s) activities after injection of GRAS for 7 days. The activities of GOT, GPT, LDH, ALP-s were decreased with GRAS. It was shown to possess considerable toxicity toward various tumor cell lines. Concentration of GRAS at 1.5g/ml and 3g/ml resulted in more than 80% inhibition of growth in Ehrlich ascites tumor cells (EATC), Hepa1c1c7, and HeLa cells. Toxicity of GRAS to A549 revealed that 68% inhibition of growth. GRWS at the concentration of 3g/ml showed more than 80% inhibition of growth with EATC, Hepalclc7, A549 and HeLa. In morphological study, the number of cells were decreased, and the shape of cells was round-form in EATC, Hepalclc7, A549 and HeLa cells with GRAS. Administration of GRAS inhibited the growth of EATC in vivo. Mice given EATC at 1.5g/ml or 0.3g/ml GRAS had 16.7% to 50% survival after 21 days. GRAS increased the proliferation of T and B cells and the cytolytic activity of purified T cell. The biosyntheses of nucleic acid and protein of EATC, Hepalclc7, A549 and HeLa cells were inhibited by GRAS.

• Journal of Veterinary Clinics
• /
• v.25 no.4
• /
• pp.249-256
• /
• 2008

This experiment was conducted to investigate antitumor and immunomodulatory effects of Artemisia capillaris extracts against Hepa-lc1c7 and Sarcoma 180 cancer cells. In in vivo experimental tests using 210 ICR mice, on the $28^{th}$ day and the $42^{nd}$ day, all animals in vehicle controled HP (Hepa-lclc7 tumor cell inoculated vehicle control) and SP (Sarcoma 180 tumor cell inoculated vehicle control) showed tumor cells in the liver and spleen based on the histopathology. However, the incidences and the percentages of regions occupied by tumor cells were dramatically and dose-dependently decreased by mACH (Artemisia capillaris methanol extracts) treatment on the histomorphometry. Although the exact mechanism of inhibition of the incidences of tumor cells in the parenchyma whether inhibition of metastasis or proliferation is unclear, mACH dramatically reduce the percentages of regions occupied by tumor cells in the liver and spleen apart from the inoculation sites of Hepa-lclc7 and Sarcoma 180. In addition, they also effectively inhibit the abnormal changes on the kidney detected in the present study. The results suggest that Artemisia capillaris methanol extracts have prominent antitumor effects on the cancer cell lines Hepa-lclc7 and Sarcoma 180 m mice.

• Korean Journal of Pharmacognosy
• /
• v.38 no.1
• /
• pp.95-99
• /
• 2007

In order to find novel cancer chemopreventive agents, quinone reductase (QR) inductive activity of methanol extract of herbal medicines was examined using murine hepatoma, hepa1c1c7 cells. QR has been used as an anticarcinogenic marker enzyme in cancer chemoprevention study. The methanol extract of Alpinia officinarum (Zingiberace) showed showed significantly strong quinone reductase inductive activity compared to the control group. The methanol extract of Alpinia officinarum was successively fractionated with various solvents according to polarity. Hexane, ethyl acetate, buthanol and water fractions were obtained and theirs activities were assessed. The QR inductive effect was moved to the ethyl acetate fraction and was highly increased. The CD (concentration required to double the specific activity of QR) value of ethyl acetate fraction was 8.6 ${\mu}g/mL$. Alpinia officinarum also showed strong antioxidant activity. These results suggest that Alpinia officinarum can be developed as cancer chemopreventive agent.

• Mycobiology
• /
• v.30 no.4
• /
• pp.213-218
• /
• 2002

The induction of NAD(P)H: quinone oxidoreductase(QR), glutathione S-transferase(GST), and glutathione(GSH) levels in hepa1c1c7 cells(murine hepatoma) by waxy brown rice cultured with Phellinus igniarius to induce anticarcinogenic enzymes were measured. In addition, the inhibition of polyamines metabolism was tested with the growth of Acanthamoeba castellanii. The result shows that QR, GST activities, and GSH levels of experimental animals were increased much more by feeding the methanol extract of waxy brown rice cultured with Phellinus igniarius than those of the rats received the ethanol of uncultured brown rice. The growth of A. castellanii was inhibited mostly at 40 mg/3 ml concentration of methanol extract of waxy brown rice cultured with P. gniarius. The results suggested that waxy brown rice cultured with P. igniarius possess chemopreventive activity by inducing anticarcinogenic enzymes and inhibiting polyamine metabolism.

• Current Research on Agriculture and Life Sciences
• /
• v.32 no.3
• /
• pp.119-124
• /
• 2014

Physalis alkekengi var. francheti Hort. is known as an insecticide and traditional remedy for liver related diseases. Therefore, this study investigated the chemopreventive effects of extracts and several solvent fractions (n-hexane, dichloromethane, n-butanol, water) of Physalis alkekengi var. francheti Hort. First, their cytotoxicity and NQO1 activity were measured using an MTT assay, plus a quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H: (quinone acceptor) oxidoreductase, EC 1.6.99.2]-inducing activity assay was performed using cultured murine hepatoma cells (Hepa1c1c7) and its mutant cells(BpRc1). The reduction of electrophilic quinones by NQO1 is an important detoxification pathway and major mechanism of chemoprevention. When compared with the other solvent soluble fractions with different polarities, the dichloromethane fraction of Physalis alkekengi var. francheti Hort. showed a higher NQO1-inducing activity that was also dose-dependent. Moreover, the dichloromethane fraction of Physalis alkekengi var. francheti Hort. induced ARE-luciferase activities in HepG2-C8 cells that were generated by transfecting the ARE-luciferase gene construct, suggesting the Nrf2-ARE-mediated induction of anti-oxidative enzymes. In conclusion, the dichloromethane-soluble fraction of Physalis alkekengi var. francheti Hort. showed a relatively strong induction of detoxifying enzymes, thereby meriting further study to identify the active components and evaluate their potential as cancer preventive agents.

• The Korean Journal of Physiology and Pharmacology
• /
• v.10 no.6
• /
• pp.349-354
• /
• 2006

The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biological and toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. The application of recombinant reporter plasmid such as the firefly luciferase gene has proven to be a very effective method to detect these chemicals. The bioassay system, CALUX, is sensitive in directly detecting AhR-agonists from a variety of environmental and biologic materials. However, responses of the AhR-dependent bioassays are dependent on the cell types used. Thus, we developed a sensitive bioassay using the recombinant mouse hepatoma cell (Hepa1c1c7) for the determination of dioxins. The recombinant cell line was stably transfected with firefly luciferase reporter gene (pGudLuc1.1). The transfected cells showed the highest induction of luciferase activity at 4.5 hr and a decrease beyond this time point. The system showed the highest sensitivity of detection ever reported. Upon TCDD exposure cells showed 2 fold increase at 10 pM and 7 fold increase at 100 pM, respectively. The passage number after the transfection played an important role in the sensitivity. The increase of passage number tended to increase the sensitivity of the cells up to 15. The media without phenol red showed a higher induction rate than with phenol red, suggesting the preferable use of phenol red-free media for the bioassay. Since each of the assays has unique characteristics that make them suitable for some screening applications and not others, development of sensitive bioanalytical methods based on a variety of cellular systems in a key to the successful determination of dioxins. The bioassay system developed in this study will contribute to further development of successful screening the AhR agonists among the environmental mixture. In addition, the rapid and sensitive nature of this cellular system can be applied as a valuable tool to screen the dioxin-like moieties among the prodrugs at the initial stage, thereby expediting the new drug discovery.