Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer cells oversecrete the lysosomal peptidase cathepsin D as a pro-enzyme. In this study, we assessed the effect of media conditioned by MRC-5 fibroblasts or MCF-7/6 breast cancer cells on cathepsin D (CD) production and secretion by these two cell types. We also considered the influence of estrogens and matrix components (type I or type IV collagen, or Matrigel) on the expression and activity of CD produced by breast cancer cells of different invasive potentials (MCF-7/AZ, MCF-7/6, MDA-MB-231). In our system, fibroblasts conditioned medium does not significantly affect CD levels produced and secreted by the MCF-7/6 cells. However, we found that fibroblasts are able to capture the pro-CD secreted by these tumor cells by a mannose 6-phosphate-dependent process. We also found a positive correlation between the proportion of extracellular CD levels and the invasive potentials of the tumor cell types considered. If estrogens are able to upregulate CD production and secretion by receptor-positive cells, it is not the case of extracellular matrix components. On the other hand, our results indicate that matrix components are able to influence the distribution of the different CD forms in and out of the cells. Our data suggest that tumor fibroblasts, by enhancing their intracellular CD levels, could assist cancer cells in the digestion of extracellular matrix during the invasion of tissues.
 ...
PMID:Fibroblasts capture cathepsin D secreted by breast cancer cells: possible role in the regulation of the invasive process. 1189 22

A new class of copper(II) nanohybrid solids, LCu(CH(3)COO)(2) and LCuCl(2), have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy, and have been found to be capped by a bis(benzimidazole) diamide ligand (L). The particle sizes of these nanohybrid solids were found to be in the ranges 5-10 and 60-70 nm, respectively. These nanohybrid solids were evaluated for their in vitro antimalarial activity against a chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2). The interactions between these nanohybrid solids and plasmepsin II (an aspartic protease and a plausible novel target for antimalarial drug development), which is believed to be essential for hemoglobin degradation by the parasite, have been assayed by UV-vis spectroscopy and inhibition kinetics using Lineweaver-Burk plots. Our results suggest that these two compounds have antimalarial activities, and the IC(50) values (0.025-0.032 microg/ml) are similar to the IC(50) value of the standard drug chloroquine used in the bioassay. Lineweaver-Burk plots for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) show that the inhibition is competitive with respect to the substrate. The inhibition constants of LCu(CH(3)COO)(2) and LCuCl(2) were found to be 10 and 13 microM, respectively. The IC(50) values for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) were found to be 14 and 17 microM, respectively. Copper(II) metal capped by a benzimidazole group, which resembles the histidine group of copper proteins (galactose oxidase, beta-hydroxylase), could provide a suitable anchoring site on the nanosurface and thus could be useful for inhibition of target enzymes via binding to the S1/S3 pocket of the enzyme hydrophobically. Both copper(II) nanohybrid solids were found to be nontoxic against human hepatocellular carcinoma cells and were highly selective for plasmepsin II versus human cathepsin D. The pivotal mechanism of antimalarial activity of these compounds via plasmepsin II inhibition in the P. falciparum malaria parasite is demonstrated.
 ...
PMID:Antimalarial evaluation of copper(II) nanohybrid solids: inhibition of plasmepsin II, a hemoglobin-degrading malarial aspartic protease from Plasmodium falciparum. 1994 19