pepstatin and Neoplasms

pepstatin has been researched along with Neoplasms* in 5 studies

Reviews

1 review(s) available for pepstatin and Neoplasms

ArticleYear
[Proteolytic enzymes and their inhibitors in clinical and experimental oncology].
    Voprosy onkologii, 1984, Volume: 30, Issue:10

    Topics: alpha 1-Antitrypsin; Animals; Aprotinin; Breast Neoplasms; Cathepsin B; Cathepsins; Cell Transformation, Neoplastic; Female; Humans; Laryngeal Neoplasms; Lung Neoplasms; Mice; Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Pepstatins; Peptide Hydrolases; Protease Inhibitors; Rats; Stomach Neoplasms

1984

Other Studies

4 other study(ies) available for pepstatin and Neoplasms

ArticleYear
Dipeptide mimic oligomer transporter mediates intracellular delivery of Cathepsin D inhibitors: a potential target for cancer therapy.
    Journal of controlled release : official journal of the Controlled Release Society, 2013, Oct-28, Volume: 171, Issue:2

    Implication of the intracellular proteolytic activity of Cathepsin D (CathD), a lysosomal aspartyl-protease overexpressed in numerous solid tumors, has been evidenced on tumor growth. Its intracellular inhibition by potent inhibitors such as pepstatin constitutes a relevant but challenging molecular target. Indeed the potential of pepstatin as a therapeutic molecule is hampered by its too low intracellular penetration. We addressed this limitation by designing and developing a bioconjugate combining a pepstatin derivative with a new vector of cell penetration (CPNP) specifically targeting the endolysosomal compartment. We showed that this pepstatin conjugate (JMV4463) exhibited high anti-proliferative effect on tumor cell cultures via intracellular CathD inhibition and altered cell cycle associated with apoptotic events in vitro. When tested in mice xenografted with breast cancer cells, JMV4463 delayed tumor emergence and growth.

    Topics: Animals; Antineoplastic Agents; Apoptosis; Biological Transport; Caspase 9; Cathepsin D; Cell Cycle; Cell Line, Tumor; Dipeptides; Female; Humans; Mice; Mice, Nude; Neoplasms; Pepstatins; Tumor Burden; Xenograft Model Antitumor Assays

2013
Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis.
    Cancer research, 2008, Jun-15, Volume: 68, Issue:12

    Cathepsin D (CD) up-regulation has been associated with human malignancy and poor prognosis. Thrombin up-regulated CD mRNA and protein in eight tumor cell lines as well as in human umbilical vascular endothelial cells (HUVEC). Thrombin increased the secretion of CD by 3- to 8-fold and enhanced chemotaxis ( approximately 2-fold) in 4T1 murine mammary CA cells, which was completely inhibited with the knockdown of CD. Secreted 4T1 CD induced neoangiogenesis by 2.4-fold on a chick chorioallantoic membrane, which was blocked in CD-KD cells. The addition of pure CD (2 ng) to the chick chorioallantoic membrane increased angiogenesis by 2.1-fold, which was completely inhibited by Pepstatin A (Pep A). CD enhanced human HUVEC chemotaxis and Matrigel tube formation by 2-fold, which was then blocked by Pep A. CD enhanced HUVEC matrix metalloproteinase 9 (MMP-9) activity by approximately 2-fold, which was completely inhibited by Pep A as well as a generic MMP inhibitor, GM6001. The injection of CD-KD 4T1 cells into syngeneic mice inhibited tumor growth by 3- to 4-fold compared with empty vector (EV) cells. Hirudin, a specific thrombin inhibitor, inhibited the growth of wild-type and EV cells by 2- to 3-fold, compatible with thrombin up-regulation of CD. CD and thrombin also contributed to spontaneous pulmonary metastasis; 4-fold nodule inhibition with CD versus EV and 4.6-fold inhibition with hirudin versus EV (P < 0.02). Thus, thrombin-induced CD contributes to the malignant phenotype by inducing tumor cell migration, nodule growth, metastasis, and angiogenesis. CD-induced angiogenesis requires the proteolytic activation of MMP-9.

    Topics: Animals; Blotting, Western; Cathepsin D; Cell Movement; Cells, Cultured; Chemotaxis; Chick Embryo; Chorioallantoic Membrane; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Hirudins; Humans; Immunoprecipitation; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Neoplasms; Neovascularization, Pathologic; Pepstatins; RNA, Messenger; RNA, Small Interfering; Thrombin; Umbilical Veins; Up-Regulation

2008
Cathepsin D overexpressed by cancer cells can enhance apoptosis-dependent chemo-sensitivity independently of its catalytic activity.
    Advances in experimental medicine and biology, 2008, Volume: 617

    The aspartic protease cathepsin D (CD) is a key mediator of induced-apoptosis and its proteolytic activity has been generally involved in this event. During apoptosis, CD is translocated to the cytosol. Since CD is one of the lysosomal enzymes that requires a more acidic pH to be proteolytically-active relative to the cysteine lysosomal enzymes such as cathepsin-B and cathepsin-L, it is therefore open to question whether cytosolic CD might be able to cleave substrate(s) implicated in the apoptotic cascade. Here, we have investigated the role of (wild-type) wt CD and its proteolytically inactive counterpart overexpressed by 3Y1-Ad12 cancer cells during chemotherapeutic-induced cytotoxicity and apoptosis, as well as the relevance of CD catalytic function. We demonstrate that wt or mutated catalytically inactive CD strongly enhances chemo-sensitivity and apoptotic response to etoposide. Both wt and mutated inactive CD are translocated to the cytosol, increasing the release of cytochrome c, the activation of caspases-9 and caspases-3 and the induction of a caspase-dependent apoptosis. In addition, pretreatment of cells with the aspartic protease inhibitor, pepstatin A, does not prevent apoptosis. Interestingly, therefore, the stimulatory effect of CD on cell death is independent of its catalytic activity. Overall, our results imply that cytosolic CD stimulates apoptotic pathways by interacting with a member of the apoptotic machinery rather than by cleaving specific substrate(s).

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Caspase 9; Catalysis; Cathepsin D; Cytochromes c; Cytosol; Drug Resistance, Neoplasm; Etoposide; Humans; Neoplasms; Pepstatins; Protease Inhibitors; Tumor Cells, Cultured

2008
In vitro stability of endogenous parathyroid hormone-related protein in blood and plasma.
    Annals of clinical biochemistry, 1994, Volume: 31 ( Pt 1)

    We describe a systematic comparison of the effects of anticoagulants, protease inhibitors and conditions of sample handling on the in vitro stability of endogenous parathyroid hormone-related protein (PTHrP) in blood from patients with hypercalcaemia of malignancy (HM). When blood was separated within 15 min of collection, PTHrP1-86 levels measured by two-site immunoradiometric assay in serum and heparinized plasma were significantly lower than in ethylenediaminetetraacetic acid (EDTA) plasma (P < 0.02). PTHrP was unstable in blood kept at 20 degrees C for 4 h and inclusion of protease inhibitors reduced, but failed to abolish, this instability. In blood collected in the presence of EDTA, inclusion of leupeptin either alone or in combination with pepstatin and aprotinin increased the mean half-time of disappearance from 3.9 to 10.1 and 11.2 h, respectively (P < 0.05). In contrast, when blood containing EDTA was separated within 15 min, PTHrP was stable in plasma at 20 degrees C for at least 4 h. As a result of the instability of PTHrP1-86 immunoreactivity in whole blood at ambient temperatures we advise that for our immunoradiometric assay (IRMA) blood collected in EDTA should be separated within 15 min, and the plasma frozen until assay.

    Topics: Anticoagulants; Aprotinin; Blood Specimen Collection; Edetic Acid; Heparin; Humans; Hypercalcemia; Immunoradiometric Assay; In Vitro Techniques; Infant; Leupeptins; Neoplasms; Parathyroid Hormone-Related Protein; Pepstatins; Peptide Fragments; Peptides; Protease Inhibitors; Temperature

1994