• The Korean Journal of Cytopathology
• /
• v.11 no.2
• /
• pp.75-81
• /
• 2000

Cathepsin D is a protease which is known to facilitate invasion and metastasis of breast carcinoma. Overexpression of cathepsin D is associated with poor clinical outcome and biologic aggressiveness of the breast cancer. We underwent immunocytochemical assay(ICA) for cathepsin D in fine needle aspiration cytology(FNAC) specimens from the breast carcinoma and benign breast diseases. In FNAC specimens cathepsin D was expressed in 21(42.9%) out of 49 cases of invasive ductal carcinoma, whereas negative result was observed in all 15 cases of benign breast diseases including 7 fibroadenomas, 6 fibrocystic diseases, and 2 benign ductal hyperplasias. Among the 11 FNAC specimens from ductal carcinoma in situ(DCIS), cathepsin D was expressed in 3 cases(27.3%). In FNAC specimens immunocytochemistry for cathepsin D showed positive result in 24 out of 60 carcinomas(sensitivity, 40%) and negative result in 15 out of all 15 benign breast diseases(specificity, 100%). No significant correlation was noted between cathepsin D expression in FNAC specimen and clinicohistological characteristics of the breast carcinoma, such as hormone receptors and cell differentiation. In conclusion, ICA of cathepsin D in FNAC specimens thought to be a good adjunct to differentiate malignancy from benign breast diseases.

• Microbiology and Biotechnology Letters
• /
• v.27 no.6
• /
• pp.458-465
• /
• 1999

Streptomyces luteogriseus KT-10 isolated from Korean farm soil produced a strong cathepsin B inhibitor. Optimal conditions for the cathepsin B inhibitor production by s. luteogriseus KT-10 were evaluated. The cathepsin B inhibitor was produced with maximal yield in the cultural condition of pH 7.0 and $25^{\circ}C$ for 4 days. Optimal medium for the cathepsin B inhibitor production was determined to be a medium containing 20g, peptone 3g, yeast extract 1g, K2HPO4 0.5g, MgSO4.7H2O 0.5g, NaNO3 0.5g, NaCl 0.5g per l. The cathepsin B inhibitor produced by S. luteogriseus KT-10 could also inhibit the other proteinases such as trypsin, papain, and cathepsin D.

• Journal of Life Science
• /
• v.19 no.11
• /
• pp.1514-1521
• /
• 2009

To evaluate the feasibility of cathepsin-B levels in preoperatively screening patients with thyroid cancer, we assigned these patients to either the thyroid cancer group (n=32) or the nodular hyperplasia group (n=7). Five healthy volunteers served as controls (n=5). We quantified cathepsin-B expressions in cancerous lesions with follicular carcinoma and hyperplastic lesions with nodular hyperplasia, and compared the degrees to those of normal thyroid tissue, which was obtained from matched contralateral lobe. The activity of serum cathepsin B was significantly higher in patients with thyroid carcinoma ($284.87{\pm}79.32$, ${\times}10^{-2}\;mU$) and those with nodular hyperplasia ($255.45{\pm}95.68$, ${\times}10^{-2}\;mU$) than compared to normal control ($168.94{\pm}15.10$, ${\times}10^{-2}\;mU$) (p<0.05). Based on the results of immunoassay, the concentrations of cathepsin B in the thyroid cancer group ($15.50{\pm}7.86\;ng/ml$) and the nodular hyperplasia group ($17.64{\pm}7.49\;ng/ml$) were higher than those of the control group ($4.85{\pm}0.61\;ng/ml$). The degree of cathepsin-B mRNA expression was significantly higher in cancerous or hyperplastic lesions than normal thyroid tissues from matched contralateral lobe with follicular carcinoma or non-neoplastic thyroid disease. Our results indicate that the activity of serum cathepsin B is a useful indicator in screening patients with nodular hyperplasia or neoplastic thyroid disease and it may be involved in the abnormal proliferation of cells.

• International Journal of Industrial Entomology and Biomaterials
• /
• v.3 no.2
• /
• pp.121-126
• /
• 2001

A cDNA encoding a cathepsin D homologue was cloned from a cDNA library of the mulberry longicorn beetle, Apriona germari. Sequence analysis of the cDNA encoding the cathepsin D homologue of A. germari revealed that the 1,158 bp cDNA has an open reading frame of 386 amino acid residues. The deduced protein sequence of the A. germari cathepsin D homologue shows high homology with cathepsin D in insects, Aedes aegypti (68.2% amino acid similarity) and Drosophila melanogaster (67.2% amino acid similarity). Two aspartic residues and six cystein residues in the A. germari cathepsin D homologue are present at identical locations in all of the other catepsins D. Unlike cathepsins D in two insect species, A. gemari cathepsin D homologue appears to have two putative glycosylation sites, rather than one. Phylogenetic analysis revealed the A. germari cathepsin D homologue is more closely related to insect cathepsins D than to the other animal cathepsins D. Northern blot analysis suggests that A. germari cathepsin D homologue gene is expressed in most if not all, body tissues.

• Development and Reproduction
• /
• v.16 no.2
• /
• pp.129-135
• /
• 2012

Previously, we identified that the overexpression of IEX-1 induces apoptosis in ovarian cancer cells. Herein we report a new binding partner of IEX-1, CATHEPSIN B, as a lysosomal enzyme which contributes to the various apoptotic signaling in tumor cells. To investigate how IEX-1 regulates cellular survival and death event, we performed yeast two-hybrid screening of rat ovarian cDNA library using IEX-1 as the bait and found CATHEPSIN B. In the present study, CATHEPSIN B and IEX-1 proteins were overexpressed in 293T cells and their specific association was determined by immunoprecipitation and immunoblot analysis. In addition, the endogenous interaction between CATHEPSIN B and IEX-1 was confirmed in HeLa cells. The current finding of lysosomal CATHEPSIN B as the IEX-1-binding partner implies that IEX-1 may involve in lysosome-mediated apoptotic signaling pathways.

• Journal of Acupuncture Research
• /
• v.22 no.3
• /
• pp.1-12
• /
• 2005

It was clarified that ethanol extract herb-acupuncture solution (EE-UD) and hydrotherapy herb-acupuncture solution (WE-UD) in Ulmus davidiana Planch (Ulmaceae), are the excellent inhibitors of cathepsin K and L. WE-UD inhibited cathepsin K when IC50 value was 5.32 ${\square}g$/ml, and suppressed cathepsin L when IC50 value was 6.34 ${\square}g$/ml. However, EE-UD indicated the activity of inhibiting cathepsin K and L in the level of 1.45 ${\square}g$/ml and 2.43 ${\square}g$/ml, thus it showed more significance than WE-UD. It could be observed that EE-VD is an excellent inhibitor to cathepsin K with Ki value of 0.8 ${\square}g$/ml. This activity is increased by 10-fold even in the analytical experiment when having operations like glutathione in pH 7.0. Also, this supports the mixture of GSH thiolate anion, thus it was thought that this increase in effectiveness is probably attributable to the enhanced chemical function in the combinations of herb-acupuncture solution towards a place of activity in enzyme. WE-UD showed the time-dependent inhibiting property, thus it allowed to know the disunion and the compounding speed in constant cathepsin K during the process of experiment. Finally, EE-UD was proved to suppress the absorbent bone ash in the experiment related to osteoclast in rats for test, and to the bone in rodent. It was proved that WE-UD has the effect of inhibiting the protease in cathepsin K and L, and in collagen of bone. These results strongly suggest that it is effective in preventing the progress of bone damage, which was induced due to cathepsin K. Also, it obtained the conclusion that it is effective to the reabsorption activity of bone in the bone marrow cells.

• Biomedical Science Letters
• /
• v.10 no.4
• /
• pp.429-434
• /
• 2004

The effects of intravenous administration of high concentration of taurocholic acid (TCA) on cathepsin B and D, and acid phosphatase activities in rat liver lysosome were studied. These liver lysosomal enzymes were determined from the experimental rats with choledocho-caval shunt (CCS). The activities of liver lysosomal cathepsin B and D, and acid phosphatase were found to be significantly increased in the CCS plus TCA injection group than in control group, such as group of CCS alone group. However, these hepatic enzyme activities did not change in the CCS plus tauroursodeoxycholic acid injection group. The above results suggest that TCA stimulates the biosynthesis of the lysosomal cathepsin B and D, and acid phosphatase in the liver.

• Journal of Acupuncture Research
• /
• v.20 no.3
• /
• pp.104-116
• /
• 2003

목적 : 시스테인 단백분해 효소인 cathepsin는 인간과 생쥐의 항원제시세포에서 II형 주적합항원 불변사슬(MHC class II invariant chain)의 분해에 관여한다. 본 연구는 녹용 약침액이 류마티스 관절염 생쥐 모델의 골조직(연골과 활액) 유래 cathepsin 활성에 미치는 영향을 검정하였다. 방법 : 관절염 동물모델은 BALb/c계 생쥐를 생후 3일에 흉선 적출(3d-Tx)을 하여 만들었다. 동물모델의 골조직, 임파절세포, 비장 등을 녹용처치군과 대조군으로 나누어 cathepsin의 활성도 및 자가항원 특이(C-II-specific) T-세포의 활성도를 비교 분석하였다. 결과 : 각 장기에서 cathepsin S의 활성은 녹용약침 처치군에서 농도 의존적으로 유의성 있게 억제되었고, T-세포 특이 자가항원반응은 녹용약침 처치군의 임파절 세포에서 유의성있게 억제되었다. 그리고 T-세포 특이 자가항원 반응의 불활성화에는 녹용 10~20ug/ml의 용량으로 충분하였다. 결론 : 이러한 실험결과는 녹용 약침액이 cathepsin S를 선택적으로 억제시켜 류마티스 관절염과 같은 자가면역 질환에 유효한 치료약물로 사용될 수 있음을 시사한다.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.21
• /
• pp.9511-9515
• /
• 2014

Cholangiocarcinoma (CCA) is a cancer of the bile duct epithelial cells. The highest incidence rate of CCA with a poor prognosis and poor response to chemotherapy is found in Southeast Asian countries, especially in northeastern Thailand and Lao PDR. Cathepsin B is a lysosomal cysteine protease which is regulated by cysteine proteinase inhibitors such as cystatin C. Elevation of cathepsin B levels in biological fluid has been observed in patients with inflammatory diseases and many cancers. We aimed to investigate the serum cathepsin B and cystatin C levels of CCA patients to evaluate the feasibility of using cathepsin B and cystatin C as markers for the diagnosis of CCA. Fifty-six sera from CCA patients, 17 with benign biliary diseases (BBD) and 13 from controls were collected and the cathepsin B and cystatin C levels were determined. In addition, cathepsin B expression was investigated immunohistochemically for 9 matched-pairs of cancerous and adjacent tissues of CCA patients. Serum cathepsin B, but not cystatin C, was significantly higher in CCA and BBD patient groups compared to that in the control group. Consistently, all cancerous tissues strongly expressed cathepsin B while adjacent tissues were negative in 7 out of 9 cases. In contrast, serum cystatin C levels were comparable between CCA and control groups, although serum cystatin C levels in the BBD group was higher than that in the control or CCA groups. When the serum cathepsin B to cystatin C ratio was calculated, that of the CCA group was significantly higher than that of the control group, and, although statistically not significant, the ratio of CCA group showed a trend to be higher than that of the BBD group. Thus, the cathepsin B to cystatin C ratio might be used as an alternative marker for aiding diagnosis of CCA.

• Food Science and Preservation
• /
• v.12 no.3
• /
• pp.275-281
• /
• 2005

This study was carried out to investigate the cathepsin B inhibition effect by Achyranthes japonica N. root extract in vitro. The methanol/$H_{2}O$(4:1, v/v) extract was fractionated by ethyl acetate(F1), chloroform(F2), chloroform/methanol(3:1, v/v)(F3) and methanol(F4). The yield of F4 in Achyranthes japonica N. root was $8.27\%$. As an index material of Achyranthes japonica N. root, 20-hydroxy ecdysone was detected by TLC, and HPLC and it's content was $0.33\%$. Three isolates(F1, F3, F4) showed the cathepsin B inhibition activity, and F4 showed the highest inhibition activity among them. In the inhibition activity on cathepsin B, leupeptin, 20-hydroxy ecdysone and F4(at the same concentration of 20-hydroxy ecdysone.) were 92, 88 and $97\%$ on BANA($N{\alpha}$-benzoyl-DL-arginine ${\beta}$-naphthylamide) substrate, and 62, 36 and $67\%$ on CLN($N{\alpha}$-CBZ(carbobenzlyoxy)-L-lysine p-nitrophenyl ester HCI) substrate, respectively.