• 제목/요약/키워드: therapeutic potential

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노화에 미치는 산소 유리라디칼에 관한 연구동향 (The involvement of oxygen free radicals in the onset of aging)

  • 김정상;나창수;김영곤
    • 한국한의학연구원논문집
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    • 제3권1호
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    • pp.229-239
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    • 1997
  • The superoxide anion radical$(O_2)$ poses a threat to macromocules and cell organelles of the living cells. This toxicity damage to all groups of proteins results in loss of enzyme function concerned with metabolism and ion transport, and peroxidation of unsaturated fatty acids and cholesterol results in a change of permeability characteristics of the membrane, and oxidative of nucleic acids results in genomic damage and thereby cause mutation, potential carcinogenesis and somatic damage that produce cellular aging Superoxide dismutase(SOD) has received substantial attention as a potential therapeutic agent. It has been investigated as a possible agent for the prevention of ontogenesis, the reduction of cytotoxic effect of anticancer drugs, and protection against damage in ischemic tissue. It is suggest that $O_2$ is concerned with cellular aging, thereafter we need to investigate herb that activated to SOD.

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적포도의 주 항산화물질, 레스베라트롤의 항암작용: 아폽토시스 의한 인체 암세포 사멸 유도 (Anticarcinogenic Activity of Resveratrol, a Major Antioxidant Presnet in Red Wine : Induction of Apoptosis in Human Cancer Cells)

  • 허연진;김정환;서효정;공구;서영준
    • 한국환경성돌연변이발암원학회지
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    • 제19권1호
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    • pp.56-62
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    • 1999
  • Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been considered to be as one of major antioxidants present in grapes responsible for beneficial effects of red wine consumption on coronary heart disease. This triphenolic stilbene has been suggested as a potential cancer chemopreventive agent based on its striking inhiitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The compound has strong antioxidative and anti-inflammatory activities which amy contribute to its chemopreventive/chemoprotective properties. In the present work, we have found that resveratrol reduces viability and DNA synthesis capability of cultured human promyelocytic leukemia (HL-60) cells. Likewise, the viability of human breast cancer cell line, MCF-7 was reduced by resveratrol treatment. The growth inhibitory and antiproliferative properties of resveratrol appear to be associated with its induction of apoptotic cell death as determined by morphological and ultrastructural changes, agarose gel electrphoretic analysis of internucleosomal DNA fragmentation, and in situ terminal end-labeling of fragmented DNA (TUNEL). This compound also inhibited the phorbol ester-induced expression of cyclooxygenase-2 (COX-2) protein in immortalized human mammary epithelial MCF-10A cells. These results suggest that resveratrol has the promising cancer therapeutic/chemopreventive potential.

Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail

  • Kim, Joo-Hyun;Park, Seoyoung;Chung, Hyewon;Oh, Sangtaek
    • BMB Reports
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    • 제48권9호
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    • pp.525-530
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    • 2015
  • Activation of the Wnt/β-catenin pathway plays a pathogenic role in age-related macular degeneration (AMD) and is thus a potential target for the development of therapeutics for this disease. Here, we demonstrated that Wnt5a antagonized β-catenin response transcription (CRT) induced with Wnt3a by promoting β-catenin phosphorylation at Ser33/Ser37/Thr41 and its subsequent degradation in human retinal pigment epithelial (RPE) cells. Wnt5a decreased the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α(TNF-α), and nuclear factor-κB (NF-κB), which was up-regulated by Wnt3a. Furthermore, Wnt5a increased E-cadherin expression and decreased cell migration by down-regulating Snail expression, thereby abrogating the Wnt3a-induced epithelial-mesenchymal transition (EMT) in human RPE cells. Our findings suggest that Wnt5a suppresses the pathogenic effects of canonical Wnt signaling in human RPE cells by promoting β-catenin phosphorylation and degradation. Therefore, Wnt5a has significant therapeutic potential for the treatment of AMD. [BMB Reports 2015; 48(9): 525-530]

LPS로 유도된 RAW 264.7 cell의 염증반응에서 MAPK 조절에 의한 가감당귀음자(加減當歸飮子)의 항염증 효과 (Effect of Gagam-Danguieumja through Regulation of MAPK on LPS-Induced Inflammation in RAW 264.7 Cells)

  • 김태연
    • 대한한방내과학회지
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    • 제34권4호
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    • pp.339-348
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    • 2013
  • Objectives : Danguieumja is a traditional medicinal prescription to treat skin disease. It was commonly used for the treatment of itching, chronic urticaria and atopic dermatitis in Korea by the addition or omission of several herbs. This study investigated the anti-inflammatory potential of Gagam-Danguieumja (GDE) water extract. Methods : We examined the effects of GDE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in a murine macrophage cell line, RAW 264.7 cells. Results : GDE inhibited production of NO in a dose dependent manner and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). As a possible molecular mechanism of anti-inflammatory effect increased phosphorylation of mitogen-activating protein kinases (MAPK) by LPS were blocked by GDE treatment. Conclusions : These results suggest that GDE has an anti-inflammatory therapeutic potential through the inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

MicroRNA-203 As a Stemness Inhibitor of Glioblastoma Stem Cells

  • Deng, Yifan;Zhu, Gang;Luo, Honghai;Zhao, Shiguang
    • Molecules and Cells
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    • 제39권8호
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    • pp.619-624
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    • 2016
  • Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all glioblastoma (GBM) cells that are in large part responsible for tumor growth and the high grade of therapeutic resistance that is so characteristic of GBM. MicroRNAs (miR) have been implicated in regulating the expression of oncogenes and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are a potential target for cancer therapy. In the current study, miR-203 expression was reduced in $CD133^+$ GBM-SCs derived from six human GBM biopsies. MicroRNA-203 transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere assay and increased expression of glial and neuronal differentiation markers. In addition, a reduced proliferation rate and an increased rate of apoptosis were observed. Therefore, miR-203 has the potential to reduce features of stemness, specifically in GBM-SCs, and is a logical target for GBM gene therapy.

Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer

  • Su, Min;Huang, Chun-Xia;Dai, Ai-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권3호
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    • pp.905-910
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    • 2016
  • Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

6-[(N-2,4-디브로모페닐)아미노]-7-클로로-5,8-퀴놀린디온의 항진균작용 및 안전성 평가 (Evaluation of Antifungal Activities and Safeties of 6-[(N-2,4-Dibromophenyl) amino]-7-Chloro-5,8-Quinolinedione)

  • 유충규;김동현;윤여표;허문영;권상미;정성희
    • 한국식품위생안전성학회지
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    • 제11권4호
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    • pp.299-306
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    • 1996
  • 6-[(N-3,4-Dibromophenyl)amino]-7-chloro-5,8-quinolinedione(FCK13) was tested for antifungal activities. The MIC values were determined by the two-fold dilution method. The therapeutic potential of RCK13 had been assessed in comparison with ketoconazole and fluconazole against systemic infections with candida albicans in normal mice. RCK13 had ED50,0.80$\pm$0.21 mg/kg but ketoconazole had ED50, 8.00$\pm$0.73 mg/kg respectively. And administered RCK13 at the ED50 for 14 days improved survival rates as well as ketoconazole. Acute oral toxicity studies of RCK13 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK13 were low and LD50 values were over 2,850 mg/kg in ICR mice. The genotoxicities of RCK13 had been evaluated. RCK13 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK13 with in vivo mouse micronucleus assay. RCK13 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK13 has no genotoxic potential under these experimental conditions.

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Epigenetic Regulation of miR-129-2 Leads to Overexpression of PDGFRa and FoxP1 in Glioma Cells

  • Tian, Xiang-Yang;Zhang, Ling;Sun, Lai-Guang;Li, Ming
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권14호
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    • pp.6129-6133
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    • 2015
  • miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.

Anti-cancer Properties of a Sesquiterpene Lactone-bearing Fraction from Artemisia khorassanica

  • Rabe, Shahrzad Taghizadeh;Emami, Seyed Ahmad;Iranshahi, Mehrdad;Rastin, Maryam;Tabasi, Nafise;Mahmoudi, Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권3호
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    • pp.863-868
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    • 2015
  • Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects. Materials and Methods: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting. Results: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c. Conclusions: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma.

Ethanol extract of Synurus deltoides (Aiton) Nakai suppresses in vitro LPS-induced cytokine production in RAW 264.7 macrophages and in vivo acute inflammatory symptoms

  • Jiang, Yunyao;Wang, Myeong-Hyeon
    • Nutrition Research and Practice
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    • 제8권1호
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    • pp.11-19
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    • 2014
  • Synurus deltoides (Aiton) Nakai, belonging to the Compositae family, is an edible plant widely distributed in Northeast Asia. In this study, we examined the mechanisms underlying the immunomodulative effects of the ethanol extract of S. deltoides (SDE). The SDE extract strongly down-regulated the mRNA expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor (TNF)-${\alpha}$, thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and TNF-${\alpha}$ in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, SDE also suppressed the nuclear translocation of the activation protein (AP)-1 and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and simultaneously decreased the phosphorylation of extracellular signal-regulated protein kinases (ERK), p38, and Akt. In agreement with the in vitro observations, the orally administered SDE ameliorated the acute inflammatory symptoms in the arachidonic acid-induced ear edema and the EtOH/HCl-induced gastritis in mice. Therefore, S. deltoides have a potential anti-inflammatory capacity in vitro and in vivo, suggesting the potential therapeutic use in the inflammation-associated disorders.