Protease inhibitors suppress in vitro growth of human small cell lung cancer.
The effect of the protease inhibitors Bowman Birk inhibitor (BBI) and aprotinin on the in vitro clonal growth of two human small cell lung cancer (SCLC) cell lines was investigated. In addition, the effect of BBI on the growth factor processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1 and 2 (PC1 and PC2) in SCLC cells was examined. The protease inhibitors BBI and aprotinin significantly decreased growth in both SCLC cell lines studied. In NCI-H345 cells, BBI appears to inhibit the processing of proGRP to GRP, as indicated by Western blot analysis. NCI-H345 cells, when treated with BBI (100 micrograms/ml), also showed highly significant decreases of mRNA for PC1 and PC2 of about 50%. These data suggest that proteases serve an important role in the growth regulation of SCLC and that inhibitors of these proteases may be potent suppressors of SCLC growth at the level of the gene.
Clark
D A
DA
Department of Pharmacology, College of Medicine, University of Arizona, Tucson.
Day
R
R
Seidah
N
N
Moody
T W
TW
Cuttitta
F
F
Davis
T P
TP
D007611:Aprotinin / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D011480:Protease Inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013381:Subtilisins / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010455:Peptides; D011480:Protease Inhibitors; D011498:Protein Precursors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; C047897:gastrin-releasing peptide precursor; D007611:Aprotinin; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases