• Toxicological Research
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• 제32권1호
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• pp.21-33
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• 2016

Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

• Journal of Dairy Science and Biotechnology
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• 제30권1호
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• pp.31-36
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• 2012

Lactobacillus rhamnosus GG(ATCC 53103) is one of the best researched probiotic strains in the world. Studies in children have shown that Lactobacillus rhamnosus GG effectively prevents early atopic disease in patients with high risk. The active molecules associated with the immunostimulatory sequence and anti-allergy effects of L. rhamnosus GG have not yet been identified. Unmethylated CpG motifs in bacterial DNA have a mitogenic effect in mouse immune cells, CpG-containing ISS oligodeoxynucleotides are potent Th1 adjuvants, effective in both preventing and reversing Th2-biased immune deviation in allergy models. The genomic DNA of L. rhamnosus GG is a potent inducer of murine B cell and dendritic cell immunoactivation. In L. rhamnosus GG genomic DNA, ID35 shows high activity in ISS assays in both mice and humans. The effects of ID35 result from a unique TTTCGTT motif located at its 5'-end, and its effects are comparable with murine prototype CpG 1826. L. rhamnosus GG is known to secrete proteinaceous pili encoded by the spaCBA gene cluster. The presence of pili structures may be essential for its adhesion to human intestinal mucus, explaining the prolonged duration of intestinal residence of this bacterium, compared to that of non-piliated lactobacilli.

• Environmental Analysis Health and Toxicology
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• 제13권1_2호
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• pp.1-9
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• 1998

The ROS-producing potency of chromium compounds of several oxidation states were determined in the H4 cells. $K_2Cr_2O_7$ as Cr (VI), synthetic Cr (V) compounds and Cr (III) as TPP produced high level of ROS. However, ROS values of Cr-picolinate as Cr (III), CrCl$_2$, CrCI$_2$, were almost equal to the control. The effects of physiological antioxidants compounds which react with free radicals were examined for their effects on chromate-induced production of reactive oxygen species (ROS) in A549 cells after the addition of $K_2Cr_2O_7$. The compounds used were vitamin C (ascorbate), vitamin E ($\alpha$-tocopherol), superoxide dismutase (SOD) and catalase. The preincubation of ascorbate (200uM) with A549 cells for 20hr resulted in a significant reduction of hexavalent chromate(100uM) induced ROS. However, there is no effects of preincubation of the cells with vitamin E succinate (10 and 20uM, 20hr) on the ROS production. Also, the effects of Cr (VI) on the cell cycle of A549 cells was measured by adding the DNA intercalating agent, propidium iodide. S phase of the cell cycle was increased by the chromium (VI) compounds up to 20uM indicating toxicity or possible mitogenic action of the cell. The shoulder in Go/G1 phase at 20uM Cr (VI) with 24 hr treatment indicates apoptosis.

• 동의생리병리학회지
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• 제21권6호
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• pp.1450-1455
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• 2007

Evodiae Fructus(EF) has been used as Traditional medicine for the treatment of headache, abdominal pain, hemorrhage, and menorrhae in many Asian countries. The present study was conducted to investigate the immunomodulatory effect on cyclophosphamide(CY)-induced immunesuppression of water extracted EF(EFE). In the mouse spleen cell proliferation assay, EFE enhanced mitogenic activity and restored the CY-induced cell suppression. In the nitric oxide(NO) assay, EFE inhibited NO production and iNOS protein levels in LPS-stimulated RAW 264.7 cells. In the GC-MS analysis, many ingredients of EFE were detected by solvents. These results indicated that EFE can modulate immune response through immune cell proliferation, the regulation of NO production and the inhibition of CY-induced immunotoxicity.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.411-418
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• 2011

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including $p27^{Kip1}$ and $p21^{WAF1/Cip1}$, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and $p70^{S6K}$. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1185-1190
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• 2008

When 10 kinds of herbal medicines were fractionated into hexane, MeOH, cold-water, and hot-water extracts, hot-water extracts from Acanthopanax senticosus (AS), Glycyrrhiza uralensis (GU), Cichorium intybus (CI), and Polygonatum odoratum (PO) showed the potent intestinal immune system modulating activity (1.72-, 1.62-, 1.60-, and 1.53-fold of control at $100{\mu}g/mL$, respectively). Especially, hot-water extracts from AS (215% compared with the control) and GU (187%) also had macrophages stimulating activity and mitogenic activity of splenocytes (7.1- and 6.5-fold) at $100{\mu}g/mL$. In addition, the effects of hot-water extracts from herbal medicines on anticancer activities were studied in mice. Hot-water extracts from AS and GU enhanced cytotoxicity of natural killer cell against cancer cell, Yac-1 (37 and 34% cytotoxicity) at E/T ratio 100:1, and colon 26-M3.1 cancer cell lines had significantly inhibited (82.1 and 75.2%) in experimental lung metastasis. These results suggest that hot-water extracts from A. senticosus and G. uralensis can be used as biological response modifiers to stimulate immune system and inhibit tumor.

• Preventive Nutrition and Food Science
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• 제2권3호
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• pp.236-240
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• 1997

A crude extract of Smphytum officinale L. (comfrey) was for its ability to inhibit he growth of hepatocellular carcinoma cells and expression of the insulin-like growth factor I (IGF-II) gene. The DNA synthesis of hepatocellular carcinoma cell lines, Hep G2, Hep 3B, and PLC/PRF/5 was inhibited by a crude extract of Smphytum officinale in both a time- and a dose-dependent manners. This plant extract also inhibited expression of the IGF-II gene. Since IGF-II exerts a mitogenic effect on Hep G2 cells, these results suggest that the growth inhibition by Symphytum officinale extract is, in part, mediated through the inhibition of IGF-II gene expression.

• 대한화장품학회지
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• 제26권1호
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• pp.17-40
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• 2000

Cytotoxicity assays using artificial skins have been proposed as in vitro alternatives to minimize animal ocular and dermal irritation testing. Accordingly, the responses of artificial skins to the well-characterized chemical irritants toluene, glutaraldehyde, and sodium lauryl sulfate (SLS), and the nonirritant polyethylene glycol were studied. The evaluation of the irritating and non-irritating test chemicals was also compared with the responses observed in human dermal fibroblasts and human epidermal keratinocytes grown in a monolayer culture. The responses monitored included an MTT mitochondrial functionality assay. In order to better understand the local mechanisms involved in skin damage and repair, the production of several mitogenic proinflammatory mediators, interleukin-l$\alpha$, 12-HETE, and 15-HETE, was also investigated. Dose-dependent increases in the levels of かIn and the HETEs were observed in the underlying medium of the skin systems exposed to the two skin irritants, glutaraldehyde and SLS. The results of the present study show that both human artificial skins can be used as efficient in vitro testing models for the evaluation of skin toxicity and for screening contact skin irritancy.

• 대한의생명과학회지
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• 제28권2호
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• pp.92-100
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• 2022

Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anti-cancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

• Journal of Periodontal and Implant Science
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• 제25권3호
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• pp.720-732
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• 1995

미분화중배엽세포의 분화에 관여한다고 알려진 변형성장인자-${\beta}1$이 초기배양한 치주인대세포와 치은섬유아세포에 각기 다른 농도와 시간에 따라 변형성장인자-${\beta}1$을 주입했을때 두 세포의 세포증식능에 미치는 영향을 알아보고 각 조건에 따른 두 세포간의 증식능을 상호 비교해 보고자 본 실험을 실시하였다. 교정치료를 목적으로 내원한 환자의 제 1 소구치 부위의 정상치은을 절제하고, 건강한 제 1 소구치를 발거하여 치은섬유아세포와 치주인대세포를 분리, 배양하여 변형성장인자-${\beta}1$을 주입시키지 않은 군을 대조군으로 하고, 변형성장인자-${\beta}1$을 각각 0.25, 0.5, 1, 2.5, 5ng/ml로 주입시킨 군을 실험군으로하여 24시간, 48시간, 72시간 동안 배양하였으며, 각 시간별 배양 24시간 전에 $1{\mu}Ci/ml$ $[^3H]-thymidine$을 첨가하여 $[^3H]-thymidine$이 DNA내로 편재되는 속도로써 두세포군의 증식능을 측정하여 다음과 같은 결과를 얻었다. DNA합성능에 미치는 변형성장인자-${\beta}1$의 효과는 치주인대세포와 치은섬유아세포 모두에서 투여한 변형성장인자-${\beta}1$의 효과는 치주인대세포와 치은섬유아세포 모두에서 투여한 변형성장인자에 대하여 농도의존적으로 세포가 증식 하는 것으로 나타났다. 치은섬유아세포에 변형성장인자-${\beta}1$을 투여한 군에서는 24, 48, 72시간 모두에서 각 대조군에 비하여 농도의존적으로 증가하는 경향을 보였다. 24시간 적용시 대조군에 비해 1,2.5, 5 ng/ml투여군에서 통계적으로 유의한 차이(P<0.05)를 나타내었고, 48시간 적용시에는 대조군에 비해 1, 2.5, 5 ng/ml 투여군에서 통계적으로 유의한 차이(P<0.05)를 나타내었다. 48시간 적용시에 가장 높은 증식능을 보였으며 72시간 적용시에는 48시간 적용에 비해 전반적으로 증식능이 감소하는 경향을 보였다. 치주인대세포의 DNA 합성능에 미치는 변형성장인자-${\beta}$의 효과는, 변형성장인자-${\beta}$를 각각 24시간, 48시간 적용하였을�� 각 대조군에 비하여 농도의존적으로 증가하는 경향을 보였으며, 24시간 적용시에 대조군에 비해 1, 2.5, 5ng/ml 투여군에서 통계적으로 유의한 차이(P<0.05)를 나타내었고, 48시간 적용시에 대조군에 비해 2.5, 5ng/ml 투여군에서 통계적으로 유의한 차이(P<0.05)를 나타애었다. 72시간 적용시에는 5ng/ml의 농도에서 증식능이 감소하는 경향을 보였다. 48시간 적용시에 역시 가장 높은 증식능을 보였으며 72시간 적용에서는 48시간 적용에 비해 전반적으로 증식능이 감소되는 경향을 나타내었다. 변형성장인자-${\beta}1$의 적용에 따른 치주인대세포와 농도별 비교에서 치은섬유아세포군이 치주인대세포군보다 더 높은것으로 나타났다.