• 폴리머
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• 제35권3호
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• pp.210-215
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• 2011

루틴은 항발암, 소염제, 항바이러스성 기능을 갖는 물질이다. 미생물이 만들어낸 폴리에스테르인 PHBV와 루틴을 전기방사하여 나노섬유 부직포를 얻었다. 나노섬유 부직포의 항균성은 황색포도상구균(Staphylococcus aureus), 폐렴간균(Klebsiella pneumoniae)을 사용하여 평가하였고, KB 셀을 이용하여 세포독성을 평가하였다. 그 결과 루틴을 3 wt% 함유할 때 지지체는 우수한 항균성을 보였으며, KB 셀을 이용한 실험결과로부터 루틴을 함유하는 PHBV 지지체는 세포독성을 나타내지 않음을 알 수 있었다.

• Archives of Pharmacal Research
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• 제29권7호
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• pp.570-576
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• 2006

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

• Nutrition Research and Practice
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• 제15권5호
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• pp.591-603
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• 2021

BACKGROUND/OBJECTIVES: Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions. MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 µM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses. RESULTS: Hesperetin (0-100 µM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment. CONCLUSIONS: Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.

• 대한통합의학회지
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• 제11권3호
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.

• Current Research on Agriculture and Life Sciences
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• 제31권1호
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• pp.51-55
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• 2013

예로부터 다양한 방면에서 약용식물로 널리 사용되어 온 감초에서 분리한 dehydroglyasperin C (DGC)는 이전의 연구에서 세포 모델계에서 비교적 높은 항산화 능력과 2상 해독효소계 활성을 유도하는 것이 확인되었으나, 동물 모델계에서 DGC의 항산화능과 2상 해독효소계를 평가하였을 때, 유의적 결과가 관찰되지 않았다. 따라서 DGC 처리시간에 따라 마우스의 장기 및 혈장에 어떠한 영향을 미치는지를 알아보고자 0, 2, 4, 6, 8, 12, 24 시간 동안 DGC를 처리한 후, 장기별 QR 유도활성과 간과 신장에서의 단백질 발현 패턴, 혈장의 항산화능력을 측정하였다. 그 결과 DGC 처리에 의한 QR 유도활성은 위, 대장에서 시간에 따라 변화하는 경향을 보였고, 간, 신장, 소장, 폐에서는 큰 경향성이 나타나지 않았으며, 2상 해독효소의 단백질 발현 패턴은 간에서는 역시 큰 경향성이 나타나지 않았고 위에서는 QR 유도활성과 유사한 경향이 나타남을 확인하였다. 혈장의 DGC 처리 시간에 따른 항산화활성은 시간에 따라 유의적으로 값이 증가한 것을 확인할 수 있었다. 결론적으로 DGC는 처리 시간에 따라 각 장기 및 혈장에 각기 다르게 영향을 미치는 것으로 사료되며, 앞으로도 추가적인 연구를 통하여 DGC의 효능을 보다 구체적으로 검증하는 것이 필요한 것으로 생각된다.

• 대한약리학회지
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• 제18권1호
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• pp.65-72
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• 1982

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.427-436
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• 2012

Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.

• 한국작물학회지
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• 제48권
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• pp.13-23
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• 2003

The trace mineral, selenium (Se), is an essential nutrient of fundamental importance to human health. It is also very toxic and can cause Se poisoning (selenosis) in human and animals when its intake exceeds a suitable amount. Se functions within mammalian systems primarily in the form of solenoprotein. About 35 selenoproteins have been identified, though many have not yet been fully elucidated. Selenoproteins contain Se as selenocyseine (Sec) and perform variety of structural and enzymic roles; the enzymic roles are best-known as the antioxidants for hydrogen peroxides and lipid peroxides, and the catalysts for production of activity thyroid hormone. Glutathione peroxidases ($\textrm{GP}_X$) among the selenoproteins prevent the generation of free radicals and decrease the risk of oxidative damage to tissues, as does thioredoxin reductase (TR). TR also provides reducing power for several biochemical processes. Selenoproteins P and W are involved with oxidant defense in plasma and muscle, respectively, A selenoprotein is also required for sperm motility and may reduce the risk of miscarriage. Some epidemiological studies have revealed an inverse correlation between Se status and cardiovascular disease, and there is considerable evidence 1mm population com-parison data and animal studies that Se is anticarcinogenic. It is also suggested that Se should be needed for the proper functioning of the immune system, and appear to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. As research continues, the role of selenium in the etiology of chronic diseases like appropriate medical nutrition therapy can be delivered and its effectiveness assessed. Se status in individuals is affected by diet and the availability of the Se. The Se content of plants is affected by the content and availability of the element in the soil in which they are grown, and so greatly varies from country to country, while the Se composition of meat reflects the feeding patterns of livestock. This paper provides an overview on Se as an essential trace mineral for human.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.339-339
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• 1994

It has been reported that Indole-3-carbinol (I3C), a naturally occurring compound In cruclferous vegetables, exerts anticarcinogenic activity In several organs In rodents. The modifying effects of I3C were therefore assessed uging a rat multi-organ carcinogenesis model. A total of 100 male Sprague-Dawley rats were divided Into 3 groups. Animals of groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., i.p.), N-methylnitrosourea (NNU; 20 mg/kg b.w., 4 times for 2 weeks, i.p), and dihydroxy-di-N-propylnitrosauine (DHPN; 0.1% In d.w. for 2 weeks) for 4 weeks (DMD treatment). Animals of groups 1 and 3 were given the diet of 0.25% I3C for 20 weeks after DMD initiation and then were given basal diet for 28 weeks. All animals were sacrificed at week 24 and 52, respectively. I3C has been clearly demonstrated promoting effects on the development of glutathione S-transferase placental form (GST-P) positive hepatic foci at 24 weeks of the experiment. And I3C also exerted promoting potential In the hepatocellular adenoma (4/14; 29%) and the adenoma (7/14; 50%) of the thyroid gland at 52 weeks of the experiment. Therefore, I3C may promote hepatocarcinogenesis and thyroid tumorigenesis in the rat multi-organ carcinogenesis model.

• BMB Reports
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• 제34권3호
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• pp.189-193
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• 2001

Curcumin a yellow pigment from Curcuma Tonga, has been known to possess antioxidative and anticarcinogenic properties, as well as to induce apoptosis in some cancer cells. There have been, however, several contradictory reports that hypothesized curcumin (a hydrophobic molecule) can bind a membrane Gpid bilayer and induce nonspecific cytotoxicity in some cell lines. Why curcumin shows these contradictory effects is unknown. In A-431 cells, growth inhibition by curcumin is due mostly to the specific inhibition of the intrinsic tyrosine kinase activity of the epidermal growth factor receptor, as reported earlier by Korutla et al. Thus, we assumed that the cell death of A-431 by curcumin might be due to the specific induction of apoptosis. In this paper we clearly show that curcumin induces apoptosis in A-431 cells. The cureumin-induced cell death of A-431 exhibited various apoptotic features, including DNA fragmentation and nuclear condensation. Furthermore, the curcumin-induced apoptosis of A-431 cells involved activation of caspase-3-like cysteine protease. Involvement of caspase-3 was further confirmed by using a caspase-3 specific inhibitor, DEVD-CHO. In another study, decreased nitric oxide (NO) production was also shown in A-431 cells treated with curcumin, which seems to be the result of the inhibition of the iNOS expression by curcumin, as in other cell lines. However, 24 h after treatment of curcumin there was increased NO production in A-431 cells. This observation has not yet been clearly explained. We assumed that the increased NO production may be related to denitrosylation of the enzyme catalytic site in caspase-3 when activated. Taken together, this study shows that the cell death of A-431 by curcumin is due to the induction of apoptosis, which involves caspase-3 activation.