• 제목/요약/키워드: cathepsin K

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Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive Properties of U87MG Glioblastoma Cells through a Possible NF-κB-Mediated Mechanism

  • Ghaffari, Seyed H.;Yousefi, Meysam;Dizaji, Majid Zaki;Momeny, Majid;Bashash, Davood;Zekri, Ali;Alimoghaddam, Kamran;Ghavamzadeh, Ardeshir
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권3호
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    • pp.1553-1564
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    • 2016
  • Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dose-dependent manner and also inhibited classical NF-${\kappa}B$ signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-${\kappa}B$ and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-${\kappa}B$ down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-${\kappa}B$-mediated inhibition of survivin and telomerase activity and NF-${\kappa}B$-dependent suppression of cathepsin B, MMP-2 and MMP-9.

OST -5440, A Small Molecule Inhibitor of Human Cathepsin K, Inhibits Bone Resorption In Vivo as well as In Vitro

  • Kim, H.D.;Park, J.H.;Lee, S.S.;H, Son-M.;Y, Kwak-W.;S, Yang-J.;I, Lim-J;Kim, S.H.;Kim, W.B.
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.133.1-133.1
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    • 2003
  • Cathepsin K (CK) is a cysteine protease that plays a major and essential role in osteoclast-mediated degradation of collagen matrix of bone. Its tissue-limited distribution and pivotal contribution to bone resorption meet the requirements as the potential therapeutic target of the disease with excessive bone loss such as osteoporosis. In a search for potent CK inhibitors. we found OST-5440 that effectively inhibited bone resorption in vivo as well as in vitro. (omitted)

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Cathepsin B & D and the Survival of Early Embryos in Red Spotted Grouper, Ephinephelus akaara

  • Gwon, Seo-Hui;Kim, Hyun Kyu;Baek, Hea Ja;Lee, Young-Don;Kwon, Joon Yeong
    • 한국발생생물학회지:발생과생식
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    • 제21권4호
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    • pp.457-466
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    • 2017
  • Survival of embryos largely depends on yolk processing during early development. Proteolytic enzymes, cathepsin B & D (ctsb & ctsd) are known to have some important roles in yolk processing of various fish species. Mature female red spotted groupers were injected with human chorionic gonadotropin (HCG) to induce ovulation. The fertilized eggs and embryos were sampled at 0, 4 and 24 HPF (hours post fertilization). Survivals of each groups of embryos were checked at 24 and 48 HPH (hours post hatching). Transcripts of ctsb & ctsd showed the highest level at 0 HPF and relatively high at 4 HPF, but greatly decreased at 24 HPF. In bad egg quality group (BE, embryos survived until 24 HPH), transcript level of ctsb at 4 HPF were significantly lower than the transcript level at the same stage in good egg quality group (GE, embryos survived until 48 HPH) while no significant change of ctsb transcript level was observed at 0 or 24 HPF between BE and GE. Transcript level of ctsd was decreased at 24 HPF, but the difference was not as strong as the case of ctsb transcript. These results suggest that maternal ctsb transcript rather than ctsd transcript is likely to be involved in egg quality resulting in the difference of survival rate of embryos at early developmental period in this species.

Peri-implant crevicular fluid levels of cathepsin-K, RANKL, and OPG around standard, short, and mini dental implants after prosthodontic loading

  • Alan, Raif;Marakoglu, Ismail;Haliloglu, Seyfullah
    • Journal of Periodontal and Implant Science
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    • 제45권5호
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    • pp.169-177
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    • 2015
  • Purpose: Despite the high success rates of endosseous dental implants, their placement is restricted according to the height and volume of bone available. The use of short or mini dental implants could be one way to overcome this limitation. Thus, this study aimed to compare standard, short, and mini dental implants with regard to associated clinical parameters and peri-implant crevicular fluid (PICF) levels of cathepsin-K (CTSK), RANK ligand (RANKL), and osteoprotegerin (OPG), after prosthodontic loading. Methods: A total of 78 non-submerged implants (Euroteknika, $Aesthetica^{+2}$, Sallanches, France) were installed in 30 subjects (13 male, 17 female; range, 26-62 years) who visited the clinic of the Periodontology Department, Faculty of Dentistry, Selcuk University. Sampling and measurements were performed on the loading date (baseline) and 2, 14, and 90 days after loading. Assessment of the peri-implant status for the implant sites was performed using the pocket probing depth (PPD), modified plaque index, modified gingival index, modified sulcular bleeding index, and radiographic signs of bone loss. PICF samples collected from each implant were evaluated for CTSK, RANKL, and OPG levels using the ELISA method. Keratinized tissue and marginal bone loss (MBL) were also noted. Results: Clinical parameters statistically significantly increased in each group but did not show statistical differences between groups without PPD. Although implant groups showed a higher MBL in the upper jaw, only the standard dental group demonstrated a statistically significant difference. At 90 days, the OPG:sRANKL ratio and total amounts of CTSK for each group did not differ from baseline. Conclusions: Within the limitations of this study, both short and mini dental implants were achieving the same outcomes as the standard dental implants in the early period after loading.

The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts

  • Kim, Yu Li;Lee, Sun Kyoung;Park, Kwang-Kyun;Chung, Won-Yoon
    • Journal of Cancer Prevention
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    • 제21권2호
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    • pp.88-94
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    • 2016
  • Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

고지방식이를 섭취한 쥐에서 눈꽃동충하초 유래 cathepsin S 저해 분획의 비만 억제 효과 (Anti-Obesitic Effects of Cathepsin S Inhibitory Fraction Derived from Paecilomyces tenuipes in Mice Fed a High-Fat Diet)

  • 허건;명길선;이정희;허철성
    • 한국식품과학회지
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    • 제41권4호
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    • pp.446-451
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    • 2009
  • Cysteine protease의 일종인 CTSS가 비만에 관여한다는 것이 알려진 후 CTSS저해를 통한 비만 억제의 가능성이 제시되고 있다. 본 연구는 눈꽃동충하초로부터 CTSS저해 활성을 갖는 분획을 분리하여 항비만 효과를 확인하는 것을 목적으로 수행되었다. 눈꽃 동충하초 열수추출물을 Diaion HP-20 수지 흡착 여부에 따라서 DHP1, DHP2 두 개의 분획으로 나누었다. CTSS에 대한 $IC_{50}$값은 열수추출물, DHP1, DHP2가 각각 108.7, 890.3, 2.3 ${\mu}g$/mL이었다. 고지방식이로 비만을 유도한 마우스에 각 분획들을 4주간 섭취시키고 체중 변화, 부고환 지방 무게, 지방세포 크기 및 혈중지질 농도 등을 측정한 결과 CTSS 저해활성이 가장 높은 분획 DHP2를 섭취시킨 실험군에서 가장 뛰어난 항비만 효능을 확인할 수 있었다. 결론적으로 본 연구는 눈꽃동충하초로부터 분리된 CTSS저해 성분들이 비만을 치료하거나 예방하는데 효과적으로 활용될 수 있는 가능성을 제시한다고 볼 수 있다. 향후 눈꽃동충하초로부터 CTSS저해 물질을 분리 및 동정한다면 보다 명확한 항비만 기작을 밝혀낼 수 있을 것이다.

RAW 264.7 세포에서 sulforaphane의 파골세포형성 저해효과 (Effects of Sulraphane on Osteoclastogenesis in RAW 264.7)

  • 황준호;이미란;강창희;부희정
    • 농업생명과학연구
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    • 제50권2호
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    • pp.151-160
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    • 2016
  • 염증성 사이토카인은 파골세포형성과정에서 중요한 요인이며, 뼈의 흡수는 자주 골다공증과 연결된다. 설포라판은 보로콜리의 화뢰로 부터 분리된 물질로 염증성 사이토카인을 억제한다고 알려져 있다. 본 실험에서는 Receptor activator of nuclear factor kappaB ligand(RANKL)로 자극된 세포에서 설포라판이 파골세포 형성 억제에 대한 효과를 측정하였다. 설포라판은 대식세포인 RAW 264.7 세포에서 파골세포 특이 마커 유전자인 tartrate-resistant acid phosphatase(TRAP), Cathepsin K, matrix metalloproteinase 9(MMP-9), calcitonin receptor을 저해하였으며, TRAP, MMP-9, tumor necrosis factor receptor-associated factor 6(TRAF6)와 전사인자인 nuclease factor of activated T cells(NFATc1)의 단백질 발현과 RANKL로 자극하였을 때 전자인사인 nuclear factor kappaB(NF-kappaB)의 전사활성도 억제 하였다. 이와 같은 결과로 설포라판이 NF-kappaB의 전사활성 억제뿐만 아니라, 파골세포형성인자(TRAP, cathepsin K, MMP-9, calcitonin, NFATc1)와 NFATc1의 발현을 억제시키는 효과가 있음을 확인하였다.