• Title/Summary/Keyword: down-regulation

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Hypopigmentary Effects of Dipeptides in B16 Melanoma Cells (디펩타이드의 B16 악성흑색종세포에서 멜라닌 생성억제작용)

  • Nam, Hee-Seung;Kim, Eun-Hyun;Kim, Su-Yeon;Lee, Hyun-E;Hong, Ji-Yun;Lee, Jae-Guk;Cho, Sung-Tai;Cho, Yang-Hwan;Yun, Hye-Young;Baek, Kwang-Jin;Kwon, Nyoun-Soo;Min, Young-Sil;Park, Kyoung-Chan;Kim, Dong-Seok
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.38 no.1
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    • pp.67-73
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    • 2012
  • In the present study, we investigated the effects of dipeptides on melanogenesis in B16 melanoma cells. It was found that WV (Trp+Val), WM (Trp+Met), and CQ (Cys+Gln) decreased melanin production dosedependently. However, dipeptides did not directly inhibit tyrosinase activity, the rate-limiting melanogenic enzyme. Therefore, we further investigated the expression of tyrosinase. Our results showed that ${\alpha}$-MSH-induced tyrosinase expression was down-regulated by WV, WM, and CQ. Thus, we propose that WV, WM, and CQ show hypopigmentary activity through tyrosinase down-regulation.

Novel DOX-MTX Nanoparticles Improve Oral SCC Clinical Outcome by Down Regulation of Lymph Dissemination Factor VEGF-C Expression in vivo: Oral and IV Modalities

  • Abbasi, Mehran Mesgari;Monfaredan, Amir;Hamishehkar, Hamed;Seidi, Khaled;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6227-6232
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    • 2014
  • Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. The aim of present study was to evaluate the efficacy of novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in terms of their potential to change the VEGF-C expression profile in a rat OSCC model. Materials and Methods: 120 male rats were divided into 8 groups of 15 animals administrated with 4-nitroquinoline-1-oxide to induce OSCCs. Newly formulated doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) and free doxorubicin were IV and orally administered. Results: Results indicated that both oral and IV forms of DOX-MTX-nanoparticle complexes caused significant decrease in the mRNA level of VEGF-C compared to untreated cancerous rats (p<0.05). Surprisingly, the VEGF-C mRNA was not affected by free DOX in both IV and oral modalities (p>0.05). Furthermore, in DOX-MTX NP treated group, less tumors characterized with advanced stage and VEGF-C mRNA level paralleled with improved clinical outcome (p<0.05). In addition, compared to untreated healthy rats, the VEGF-C expression was not affected in healthy groups that were treated with IV and oral dosages of nanodrug (p>0.05). Conclusions: VEGF-C is one of the main prognosticators for lymph node metastasis in OSCC. Down-regulation of this lymph-angiogenesis promoting factor is a new feature acquired in group treated with dual action DOX-MTX-NPs. Beside the synergic apoptotic properties of concomitant use of DOX and MTX on OSCC, DOX-MTX NPs possessed anti-angiogenesis properties which was related to the improved clinical outcome in treated rats. Taking together, we conclude that our multifunctional doxorubicin-methotrexate complex exerts specific potent apoptotic and anti-angiogenesis properties that could ameliorate the clinical outcome presumably via down-regulating dissemination factor-VEGF-C expression in a rat OSCC model.

Anticancer Effects of Thymoquinone, Caffeic Acid Phenethyl Ester and Resveratrol on A549 Non-small Cell Lung Cancer Cells Exposed to Benzo(a)pyrene

  • Ulasli, Sevinc Sarinc;Celik, Sefa;Gunay, Ersin;Ozdemir, Mehmet;Hazman, Omer;Ozyurek, Arzu;Koyuncu, Tulay;Unlu, Mehmet
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6159-6164
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    • 2013
  • Background: Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro. Materials and Methods: The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups. Results: TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004). Conclusions: Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.

Ameliorating Effects of Lactic Acid-fermented Garlic Extracts on Oleic Acid-induced Hepatic Steatosis (유산균 발효 마늘 추출물의 oleic acid로 유도된 비알코올성 지방간에 대한 개선 효과)

  • Lee, Hee-Seop;Lim, Won-Chul;Choi, Ji-Hwi;Yu, Heui-Jong;Kim, Ki-Ho;Lee, Seung-Hyun;Cho, Hong-Yon
    • Korean Journal of Food Science and Technology
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    • v.46 no.6
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    • pp.762-768
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    • 2014
  • In this study, the ameliorating effects of lactic acid-fermented garlic extract (LAFGE) on non-alcoholic fatty liver were investigated using oleic acid-induced steatotic HepG2 cells. The ameliorating mechanism was analyzed by RT-PCR and Western blot. Treatment with 1 mg/mL LAFGE decreased intracellular lipid accumulation approximately 1.5-fold, compared to that achieved with non-fermented garlic extract. LAFGE reduced fatty acid influx into hepatocytes through down-regulation of FAT/CD36 mRNA expression in the steatotic HepG2 cells. $PPAR{\alpha}$ and CPT-1 mRNA expression was significantly up-regulated by LAFGE treatment of HepG2 cells as a consequence of activation of beta oxidation. Additionally, the treatment with 1 mg/mL LAFGE highly down-regulated mRNA expression of SREBP-1c and FAS to 51% and 35%, respectively. LAFGE showed concentration-dependent down-regulation patterns in protein expression of SREBP-1c and FAS, as determined by Western blot. These results suggest that LAFGE treatment improves hepatic steatosis triggered by the imbalance of hepatic lipid metabolism owing to oleic acid treatment.

Effects of Camellia sinensis Extracts on the Antioxidant System and Alcohol Down-Regulation Enzymes in Sub-Acute Ethanol Treated ICR Mice (차나무(Camellia sinensis) 추출물이 아급성 알코올 투여 마우스의 항산화 및 알코올 분해 효소 활성에 미치는 영향)

  • Koo, Sung-Ja;Choi, Il-Sook;Kong, Yeon-Hee;Choi, Sang-Yoon;Jo, Youn-Ock
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.9
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    • pp.1134-1139
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    • 2007
  • This study was conducted to investigate the effects of four kinds of tea (Camellia sinensis) extracts on the antioxidant defense systems as well as the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in ethanol administered ICR mice. According to the results, treatment with puerh tea significantly increased the superoxide dismutase activity and glutathion reductase activity in liver. In addition, the group treated with oolong tea exhibited higher superoxide dismutase activity and glutathion reductase activity in serum than those of puerh tea, green tea and black tea treated groups. The oolong tea and puerh tea also reduced malondealdehyde contents in both liver and serum. These results suggested that puerh tea and oolong tea were the most effective against alcohol-induced oxidative damage among the Camellia sinensis teas. On the other hand, in the measurement of alcohol break-down enzyme activities, the group treated with green tea exhibited the highest hepatic ADH and ALDH activities, suggesting that the group treated with green tea might be useful for alcohol down-regulation.

An Exploratory Content Analysis of Beer Advertisements in Korea (국내 주류광고에 대한 탐색적 연구: 동영상 맥주광고 내용분석)

  • Lee, Jae-Kyoung;Chung, Sul-Ki;Park, Jae-Eun
    • Korean Journal of Health Education and Promotion
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    • v.29 no.2
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    • pp.47-58
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    • 2012
  • Objectives: The purpose of this study is to analyze contents of beer advertisements in Korea. Research has suggested the influence of alcohol advertisements on viewer's drinking behavior, attitude, and expectancies. Korea's policy on alcohol advertising relies on limited government regulation and self regulation among alcohol industries. This study is expected to lay a foundation for further discussion on regulating alcohol advertising in Korea. Methods: A total of 81 beer advertisements broadcasted between 2008 and 2011 were analyzed. The contents were categorized into themes (22 themes were used), models, and presentation techniques. Results: The themes most frequently appeared in beer advertisements were quality (66.7%), relaxation (44%), camaraderie (41%), and individuality (39.5%), respectively. Analysis of models revealed that most advertisements had more than three models (64.2%), and most of them were in their 20s (68%). As much as 82% of advertisements used celebrity models. Analysis on presentation techniques showed that 91.4% displayed drinking scenes, and 27% displayed gulping down the whole bottle or the glass. Finally, about 10% of ads showed drinking in hazardous situations such as during water sports. Conclusion: The results of the study reflect the minimal regulation of alcohol advertising in Korea. The need for joint effort by legislators, researchers, alcohol industries, and advertising agencies is discussed in order to establish healthier drinking environment.

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

  • Xue, Xia;Yu, Jin-Long;Sun, De-Qing;Kong, Feng;Qu, Xian-Jun;Zou, Wen;Wu, Jing;Wang, Rong-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3987-3992
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    • 2014
  • Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

Regulation of PPAR and SREBP-1C Through Exercise in White Adipose Tissue of Female C57BL/6J Mice

  • Jeong, Sun-Hyo
    • Biomedical Science Letters
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    • v.18 no.3
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    • pp.227-236
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    • 2012
  • Previous study showed that swimming improved obesity but was not through $PPAR{\alpha}$ activation in liver and skeletal muscle in high fat diet-fed female mice with functioning ovaries as an animal model of obese premenopausal women. Thus, this study was aimed at investigation of the effects of swimming on the promotion of health and its molecular mechanism in adipose tissue of high fat diet-fed female mice. Eight-week-old female C57BL/6J mice were randomly divided into two groups (a non-swim control group and a swim group, n=8/group). Mice in the swim group swam for 2 h daily for 6 weeks in water bath with temperature of $35{\pm}1^{\circ}C$. All the animals received high fat diet (45% kcal fat) for 6 weeks. Reverse transcription-polymerase chain reaction was used to elucidate the molecular mechanism. Female mice subjected to swimming had significantly decreased body weight gain and white adipose tissue mass compared with the female control mice. Histological studies illustrated that swimming decreases the hepatic lipid accumulation. As expected, swimming did not affect the expression of mRNA levels of peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 and medium chain acyl-CoA dehydrogenase in the white adipose tissue. However, mice that underwent 6-weeks of swimming exercise had decreased the mRNA expression of lipogenic genes, such as sterol regulatory element-binding proteins-1C and fatty acid synthase in comparison to sedentary control mice, with decreased $PPAR{\gamma}$ target genes involved in adipocyte-specific marker genes, such as adipocyte fatty acid binding protein and leptin in the white adipose tissue. These results suggest that swimming can effectively prevent obesity induced by high fat diet-fed, in part through down-regulation of adipogenesis and lipogenesis in white adipose tissue of female obese mice. Moreover, these results suggest that swimming maybe contributing the promotion of health through regulation of adipogenesis and lipogenesis in overweight premenopausal women.

Effect of S-Allyl Cysteine(SAC) on the Proliferation of Umbilical Cord Blood(UCB)-derived Mesenchymal Stem Cells(MSCs) (S-Allyl Cysteine(SAC)이 제대혈 유래 중간엽 줄기세포 증식에 미치는 영향)

  • Park, Ran-Sook
    • The Korean Journal of Food And Nutrition
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    • v.22 no.2
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    • pp.313-319
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    • 2009
  • To improve the growth of human mesenchymal stem cells(hMSCs) under general cell culture conditions(20% $O_2$ and 5% $CO_2$), we examined the effect of s-allylcysteine(SAC), which is known as an antioxidant and the main component of aged-garlic extract, on hydrogen peroxide-induced cellular stress in hMSCs. We found that SAC blocked hydrogen peroxideinduced cell death and cellular apoptosis, but that SAC did not improve the growth of hMSCs during short-term culture. To evaluate the protective effect of SAC, we examined the endogenous expression of the antioxidant enzymes catalase (CAT), superoxide dismutase(SOD), and glutathione peroxidase(Gpx) in hMSCs. Hydrogen peroxide was found to downregulate the expression of CAT, SOD, and Gpx at the protein level. However, in the pre-treatment group of SAC, SAC inhibited the hydrogen peroxide-induced down-regulation of CAT, SOD, and Gpx. Unfortunately, treatment with SAC alone did not induce the up-regulation of antioxidant enzymes and the cell proliferation of hMSCs. Surprisingly, SAC improved cell growth in a single cell level culture of hMSCs. These results indicate that SAC may be involved in the preservation of the self-renewal capacity of hMSCs. Taken together, SAC improves the proliferation of hMSCs via inhibition of oxidative-stress-induced cell apoptosis through regulation of antioxidant enzymes. In conclusion, SAC may be an indispensable component in an in vitro culture system of human MSCs for maintaining self-renewal and multipotent characterization of human MSCs.

Influence of Gungguitang-gamibang on the Regulation of Melanogenesis through JNK Signaling Pathway in B16 Melanoma Cells

  • Jeong, Jae-Seong;Ju, Sung-Min;Kim, Kun-Jung;Kim, Eun-Cheol;Park, Hyun;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.1
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    • pp.196-203
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    • 2005
  • Gunggui-tang has been used for the therapy of blood disorders in Hangbang medicine for long time. Also, Glycyrrhiza uralensis has been used for deficientblood patterns with an irregular pulse or palpitations, coughing and wheezing, and heat or cold in the lungs. Melanogenesis is a physiological process resulting in the synthesis of melanin pigments. We investigated whether the water extract of Gunggui-tang plus G. uralensis inhibited melanogenesis in B16 melanoma cells. Because the molecular events connecting the regulation in tyrosinase activity remain to be elucidated, we also aimed to determine whether Gunggui-tang gamibang(GTG) affects tyrosinase at the gene activation level in the cells. First, we showed that GTG inhibited the tyrosinase promoter activity and further, down-regulated the tyrosinase protein activity in ${\alpha}-melanocyte-stimulating$ hormone $({\alpha}-MSH)-treated$ B16 melanoma cells. GTG also resulted in a decrease of melanin content in MSH-induced melanogenesis, indicating that GTG may be a useful drug in studying the regulation of melanogenesis. The pretreatment of GTG significantly prevented phosphotransferase activity of c-Jun N-terminal kinase (JNK1) and transcriptional activation of activating protein-1 (AP-1) in MSH-treated B16 melanoma cells. These findings indicate that GTG inhibits melanogenesis of B16 melanoma cells via suppression of phosphotransferase activity of JNK1 and transcriptional activation of AP-1.