• Title/Summary/Keyword: anticancer activities

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The Effect of Uteroglobin on cPLA2, COX-2 Expression and ERK Activation in NSCLC Cells (비소세포 폐암세포에서 Uteroglobin의 이입에 의한 cPLA2와 COX-2 발현 및 ERK 활성의 변화)

  • Kim, Woo Jin;Yoon, Jung Min;Lee, Kyoung Hee;Han, Seon Jin;Shin, Won Hyuk;Yim, Jae-Joon;Yoo, Chul-Gyu;Lee, Choon Taek;Han, Sung Koo;Shim, Young-Soo;Kim, Young Whan
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.6
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    • pp.638-645
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    • 2004
  • Background : Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines. Methods : The A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirusuteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography. Results : Western blot revealed decreased expression levels of cPLA2, and COX-2, and increased pERK levels in nonsmall cell lung cancer cells after uteroglobin overexpression. Zymography revealed no changes in the MMP-2 activity and lower MMP-9 activity. U0126, which is a specific inhibitor of ERK-activating kinase MEK-1/-2, prevented the decrease in the MMP-9 activity Conclusions : A decrease in cPLA2 expression, COX-2 expression, MMP-9 activity and a increase in ERK activity may be related to the anticancer effects of uteroglobin in nonsmall cell lung cancer cells.

Chemical Composition and Antiproliferative Activity of Supercritical Extract of Immature Citrus Peel in human cervical carcinoma HeLa cells (미성숙 감귤 과피 초임계 추출물의 성분 분석과 자궁암세포 성장억제효능)

  • Moon, Jeong Yong;Song, YeonWoo;Hyun, Ho Bong;KimCho, Somi
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.12
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    • pp.8836-8843
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    • 2015
  • This study was performed to investigate the antiproliferative activities of supercritical extracts from phalsak(Citrus hassaku Hort ex Tanaka) and yeagam(Citrus iyo Hort. ex Tanaka) against human cervical carcinoma HeLa cells and the chemical compositions of the extracts. The anticancer properties of supercritical extracts were demonstrated using the MTT assay and Hoechst 33342 staining and the compositional analyses were conducted by using gas chromatography-mass spectrometry(GC-MS). The peel extracts of both species exhibited similar antiproliferative effect. The antiproliferative activity of the flesh extracts was not detected up to $400{\mu}g/mL$, whereas peel extracts of phalsak and yeagam reduced cell viability with 87.16% and 92.95% at $400{\mu}g/mL$, respectively. There was a dramatic increase of the apoptotic body formation in the cell treated with peel extracts while no apoptotic body formation detected in the cell treated with flesh extracts at 100, $200{\mu}g/mL$. By GC-MS analysis, 27 and 31 kinds of compounds identified in flesh and peel of phalsak, while 27 and 29 kinds of compounds were identified in flesh and peel of yeagam, respectively. 1,1,4,4-Tetramethyl-2-tetralone(20.86%), alloimperatorin(8.15%), limonene(11.23%), and auraptene(7.29%) were major in peel of phalsak, whereas limonene(22.19%), linalool(11.23%), and ${\gamma}$-sitosterol(9.12%) were major in peel of yeagam.

Biological Activity of Ixeris dentata Nakai juice Extracts (씀바귀(Ixeris dentata Nakai) 생즙 추출물의 생리활성)

  • 김명조;김주성;강원희;조미애;함승시;정동명
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.5
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    • pp.924-930
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    • 2002
  • Ixeris dentata extracts exllibited antimicrobial activity against some bacteria and fungi. Also EtOH extracts showed strong antioxidant activity and RC$_{50}$ value was 28 $\mu\textrm{g}$/mL. The inhibitory effect of Ixeris dentata on the mutagenicity in Salmonella and cytotoxicity on cancer cell were studied. Ixeris dentata extracts showed anti-mutagenic effects of 78.83 and 75.96% on B(a)P in S. typhimurium TA98 and Th100, respectively. These extracts showed 78.72% antimutagenicity on TA100 against MNNG. The Ixeris dentata extract with strong antimutagenic activities was further fractionated by hexane, ethyl acetate, butanol and water. Butanol fraction was found to be highest in antimutagenic activity against MNNG than the other fractions. Butanol fraction of Ixreis dentate revealed the highest cytotoxicity against AS49 human lung carcinoma cells in which cell growth was inhibited by 93.75% at 375 $\mu\textrm{g}$/mL. Hexane fraction of ixeris dentate exhibited 68.56% inhibition against MCF-7 human breast adenocarcinoma cells at 500 $\mu\textrm{g}$/mL. Hexane fraction of Ixeris dentata exhibited 84.91% inhibition against Hep 3B human hepatocellular carcinoma cells at 500 $\mu\textrm{g}$/mL. From these results, it is considered that Ixeris dentata has strong antimutagenic and anticancer effects in vitro. However, these extracts and fractions did not show any cytotoxic effect against 293 cells.

Inhibitory Effects of Spinach, Cabbage, and Onion Extracts on Growth of Cancer Cells (시금치, 양배추, 양파 추출물의 암세포 증식 억제 효과)

  • Lee, Hae-Nim;Shin, Seong-Ah;Choo, Gang-Sik;Kim, Hyeong-Jin;Park, Young-Seok;Kim, Sang-Ki;Jung, Ji-Youn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.5
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    • pp.671-679
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    • 2016
  • Extracts from spinach, cabbage, and onion are known to possess various instructive characteristics, including antioxidant and anti-inflammation activities. Spinach, cabbage, and onion are consumed worldwide and represent important sources of dietary phytochemicals with proven antioxidant properties, such as flavonoids and phenolic acids. Food-derived flavonoids and phenolic compounds are expected to be promising drugs for cancer. In the present study, we investigated the effects of methanol extracts of spinach, cabbage, and onion on cell proliferation and apoptosis in human gastric and breast cancer cells. Proliferation rates of AGS, MDA-MB-231, and SK-BR-3 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The methanol extracts of spinach, cabbage, and onion inhibited proliferation of cancer cells in a dose-dependent manner. 4',6-Diamidino-2-phenylindole (DAPI) staining revealed that chromatin condensation significantly increased compared with the control. In the results of MTT assay and DAPI staining, onion extract was the most effective in inhibiting cancer cell proliferation and apoptosis. To assess changes in protein expression level by onion extract, we identified Bax (pro-apoptotic), Bcl-2 (anti-apoptotic), and poly(ADP-ribose) polymerase (PARP) protein by western blot analysis. The expression of Bax and cleaved-PARP increased, whereas expression of Bcl-2 was decreased compared with the control. These results suggest that spinach, cabbage, and onion extracts suppressed growth of human gastric cancer AGS, human breast cancer MDA-MB-231, and SK-BR-3 cells through induction of apoptosis. Among the extracts, onion extract had stronger anti-cancer and apoptosis induction effects than spinach and cabbage extracts. Further, onion extract more effectively induced apoptosis of human gastric cancer cells than human breast cancer cells. Therefore, further studies are needed to determine the anti-cancer effects of onion extracts in vivo. Onion extract can be developed as a chemopreventive or therapeutic agent for gastric cancer.

The Food Safety of Superfine Powder (Phellinus linteus) Processed by Nanomill in C57BL/6 Mice (C57BL/6 마우스에서 나노밀 가공된 초미세분말(상황버섯)의 식이 안전성 연구)

  • Kim, Dong-Heui;Teng, Yung-Chien;Yoon, Yang-Sook;Qi, Xu-Feng;Jeong, Hyun-Seok;Joo, Kyung-Bok;Lee, Kyu-Jae
    • Applied Microscopy
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    • v.39 no.2
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    • pp.133-139
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    • 2009
  • A officinal mushroom, Phellinus linteus (PL) has been known to exhibit potent biological activities including antioxidative and anticancer effect. PL is consumed as a type of powder or extract for the purpose of health promotion and disease treatment. Recently superfine PL products was commercialized according to the development of pulverizing technology such as nanomill, so the evaluation of food safety is suggested. This study was conducted to evaluate the food safety of superfine PL (SPL) through hematological, biochemical and histological examination in mice as compared with fine PL (FPL). In the particle size distribution in volume after nanomill processing, the mean diameter of SPL and FPL particles was 11.78 ${\mu}m$ and 216.1 ${\mu}m$, and d (0.5), the particle diameter measured at 50% of distribution was 5.5 ${\mu}m$ and 147.9 ${\mu}m$, respectively. As the result of body weight, food intake and the weight of organs, SPL group didn't show any statistical difference compared with FPL group and normal group (N). Hematological and biochemical values were also involved in the normal range, although ALT (N vs. FPL, P<0.001) and BUN (N vs. FPL, P<0.01; N vs. SPL, P<0.01) showed significance compared with N group but there are no significance between FPL and SPL group. In the result of histological examination with liver, kidney, spleen, and small and large intestine, abnormal findings such as inflammatory reaction and histological changes were not observed. Our results suggest that the oral intake of SPL diet is not harmful to the animal in the hematological, biochemical and histological aspects although particle size was reduced to the level of superfine. However, further study will be necessary to confirm the histological safety in relation to the gastrointestinal contact of superfine particles in the case of large amount and long-term intake.

Induction of Apoptosis and Antitumor Activity by Stichoposide D through the Generation of Ceramide in Human Leukemia Cells (Stichoposide D의 백혈병 세포주에서 세라마이드 생성을 통한 세포 사멸 유도 및 항암 작용)

  • Park, Eun-Seon;Yun, Seung-Hoon;Shin, Sung-Won;Kwak, Jong-Young;Park, Joo-In
    • Journal of Life Science
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    • v.22 no.6
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    • pp.760-771
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    • 2012
  • Marine triterpene glycosides are physiologically active natural compounds isolated from sea cucumbers(holothurians). It was demonstrated that they have a wide range of biological activities, including antifungal, cytotoxic, and antitumor effects. A previous study showed that stichoposide C (STC) isolated from Thelenota anax induces apoptosis through generation of ceramide by activation of acid sphingomyelinase (SMase) and neutral SMase in human leukemia cells. In this study, we investigated whether STD, a structural analog of STC, can induce apoptosis and examined the molecular mechanisms for its activity. It was found that STC and STD induce apoptosis in a dose- and time-dependent manner and lead to the activation of caspase-8, mitochondrial damage, activation of caspase-9, and activation of caspase-3 in K562 and HL-60 cells. STC activates acid SMase and neutral SMase, which results in the generation of ceramide. Specific inhibition of acid SMase or neutral SMase partially blocked STC-induced apoptosis, but not STD-induced apoptosis. In contrast, STD generates ceramide through the activation of ceramide synthase. Specific inhibition of ceramide synthase partially blocked STD-induced apoptosis, but not STC-induced apoptosis. Moreover, STC and STD markedly reduced tumor growth of HL-60 xenograft tumors and increased ceramide generation in vivo. These results indicate that STC and STD can induce apoptosis and have antitumor activity through the different molecular mechanisms, because they have a different sugar residue attached to aglycones. Thus, these results suggest that their actions are affected by a sugar residue attached to aglycones and they can be used as anticancer agents in the treatment of leukemia.

Inhibition of Adipocyte Differentiation and Adipogenesis by Aged Black Garlic Extracts in 3T3-L1 Preadipocytes (흑마늘 추출물에 의한 3T3-L1 지방전구세포의 분화 및 adipogenesis 억제에 관한 연구)

  • Park, Jung-Ae;Park, Cheol;Han, Min-Ho;Kim, Byung-Woo;Chung, Yoon-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.5
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    • pp.720-728
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    • 2011
  • Garlic (Allium sativum) has been used as a source food as well as a traditional folk medicine ingredient since ancient times. Aged black garlic is a type of fermented garlic and is expected to have stronger anticancer and antioxidant activities than raw garlic. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis are poorly understood. In the present study, the effects and mechanisms of water extracts of raw garlic (WERG) and aged black garlic (WEABG) on adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes were investigated. Treatment with WEABG significantly suppressed terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining, however WERG had no such effect. In addition, WEABG reduced accumulation of cellular triglyceride, which is associated with a significant inhibition of key pro-adipogenic transcription factors including peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ (C/EBP${\alpha}$) and C/EBP${\beta}$. Taken together, these results provide important new insight that aged black garlic might inhibit adipogenesis by suppressing the pro-adipogenic transcription factors in 3T3-L1 preadipocytes, and further studies will be needed to identify the active compounds that confer the anti-obesity activity of aged black garlic.

EFFECT OF CURCUMIN AND RESVERATROL ON THE CELL CYCLE REGULATION, APOPTOSIS AND INHIBITION OF METASTASIS RELATED PROTEINS IN HN-4 CELLS (Curcumin과 resveratrol에 의한 두경부암 유래의 HN-4 세포의 세포주기, 세포사 및 전이관련 단백질의 발현 조절)

  • Kim, Sa-Yub;Lee, Sang-Han;Kwon, Taeg-Kyu
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.29 no.5
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    • pp.272-281
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    • 2003
  • Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.

An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • v.8 no.1
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

Protective Effect of Functional Perilla frutescens Hot-water Extract Against tert-butyl hydroperoxide-Induced Liver Oxidative Damage in Rats (랫드에서의 t-BHP 유발 산화스트레스에 대한 기능성 들깻잎 열수 추출물의 간 보호 효과)

  • Yang, Sung-Yong;Kang, Jeong-Han;Lee, Kwang-Won
    • Journal of Food Hygiene and Safety
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    • v.28 no.2
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    • pp.146-151
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    • 2013
  • Perilla frutescens usually dieted in East Asian country such as Korea and Japan. Antioxidant, antiinflammatory and anticancer activities of perilla leaves have been founded. In previous study, we confirmed that caffeic acid, major compound of perilla, was accumulation by sucrose aqueous solution and thus antioxidant effect of perilla was enhanced. In this study, we investigated the protective effect of functional perilla leaves extract (PLE) against tert-butyl hydroperoxide(t-BHP) induced-oxidative hepatotoxicity. The pretreatment with PLE (250, 500 and 1000 mg/kg b.w.) for 5 days before a single dose of t-BHP (i.p.; 0.5 mmol/kg) significantly lowered the serum levels of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase dose-dependently. And we confirmed that the indicators of oxidative stress were remarkably reduced in the liver, such as the glutathione contents and malondialdehyde, marker of lipid peroxidation. Pathological histology of the rat livers tissues showed that PLE reduced the hepatocyte degeneration and neutrophilic infiltration of liver induced by t-BHP. These results suggest that functional perilla frutescens has the protective effect of liver against t-BHP-induced oxidative hepatic stress in rats.