Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury, when injected in high concentration. In the present study, we investigated the mechanisms for the cytotoxicity of GM on porcine aorta endothelial cells (PAECs). GM (0.5 - 5.0 mM) decreased cell viability in a dose-dependent manner and caused cell injury, whilst nafamostat mesilate (NM), another serine protease inhibitor, or mesilate itself had no effect on cell viability. zVAD-fmk, a pancaspase inhibitor, or zDEVD-fmk, a caspase-3 inhibitor, did not affect the GM (1.5 mM)-induced decrease of cell viability. Apoptotic cells or DNA fragmentation were also not observed after GM treatment. Moreover, Ca(2+) chelators, a nitric oxide (NO) synthase inhibitor, antioxidants, and radical scavengers had no effect on the GM-induced cell injury. On the other hand, cellular ATP content was decreased in the GM (2.0 mM)-treated cells. Surprisingly, GM (2.0 mM) immediately increased cellular uptake of propidium iodine. These findings suggest that GM induces necrotic cell death via injury of the cell membrane.
 ...
PMID:Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells. 1831 64

Many anticancer drugs are developing until now. However, conventional anticancer drugs causes damage to not only cancer cells but also non-cancerous tissues and cells. Therefore, the development of new drugs are anticipated.HepG2 cell proliferation in cell culture was significantly inhibited by gabexate mesilate. In TUNEL method, a significant amount of HepG2 cells cultured with gabexate mesilate showed a decrease in the number of total cells and an increased in the number of positive cells. Further immunohistochemical staining for P-53,ss-DNA and caspase 3 showed samely a decrease in the number of total cells and an increase in the number of positive cells. The staining for bcl2 showed a decrease in the number of total cells and no remarkable change in the number of positive cells. The cell growth inhibition by gabexate mesilate was almost blocked by caspase 3 inhibitor. Therefore, the inhibition itself of HepG2 cell proliferation by gabexate mesilate was mainly due to the apoptosis. This agent causes mainly damage to HepG2 cell by apoptosis but does not cause side effects, differing from the above anticancer drugs, Gabexate mesilate is a useful drug.
 ...
PMID:The specific inhibition of HepG2 cells proliferation by apoptosis induced by gabexate mesilate. 2083 Feb 42