Observations on the inhibition of serum and cell surface enzymes by eicosapentaenoic acid.
The relationship between serum and tumour cell surface proteolytic enzymes and the development of muscle breakdown in cancer cachexia has been studied in a murine model of the condition (MAC16). The surface of the MAC16 tumour cells carried a proteolytic enzyme referred to as guanidinobenzoatase (GB). Serum from mice also contained an enzyme (referred to as MSE) which cleaved the trypsin inhibitor 4-methylumbelliferyl-p-guanidinobenzoate as a true substrate, but there was no relationship with weight loss or the presence or absence of tumour and the level of this serum enzyme. Polyunsaturated fatty acids (PUFAs) were shown to be inhibitors of MSE at microM concentrations and one PUFA, eicosapentaenoic acid (EPA) was found to be a non-competitive inhibitor of both MSE and GB. The effect of EPA was specific since other proteolytic enzymes, trypsin, esterase and tissue plasminogen activator were unaffected by concentrations inhibiting GB and MSE. MSE and GB are two different enzymes which possess some common properties. However, GB is likely to be significant for tumour development since MSE is also found in normal mouse serum.
Smith
K L
KL
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Steven
F S
FS
Tisdale
M J
MJ
D000818:Animals; D002100:Cachexia / Q000201:enzymology* / Q000209:etiology; D002265:Carboxylic Ester Hydrolases / Q000097:blood / Q000187:drug effects*; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology*; D010450:Endopeptidases / Q000097:blood / Q000187:drug effects*; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000150:complications* / Q000201:enzymology; D012235:Rhodamines / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000187:drug effects; D015431:Weight Loss
C017532:4-methylumbelliferylguanidinobenzoate; D008565:Membrane Proteins; D012235:Rhodamines; D006923:Hymecromone; C037981:N-benzyloxycarbonylargininamidorhodamine; D015118:Eicosapentaenoic Acid; D002265:Carboxylic Ester Hydrolases; C037288:guanidinobenzoate esterase; D010450:Endopeptidases; D010959:Tissue Plasminogen Activator