Role of lysosomal cathepsins in naphthazarin- and Fas-induced apoptosis in oral squamous cell carcinoma cells.
CONCLUSIONS
Intracellular cysteine cathepsins are pro-apoptotic factors involved in activation of caspases in two oral squamous cell carcinoma (SCC) cell lines.


OBJECTIVE
To study the possible involvement of lysosomal cathepsins in oral SCC cell apoptosis.


METHODS
Apoptosis was induced in the two human oral SCC cell lines UT-SCC-20A and UT-SCC-24A using naphthazarin or anti-Fas antibodies, and was studied by analysis of caspase activity and nuclear morphology. Involvement of lysosomal cathepsins was investigated using the cysteine cathepsin inhibitor z-FA-FMK and the cathepsin D inhibitor pepstatin A. The amounts of cellular and soluble Fas death receptor were determined by ELISA.


RESULTS
Release of cathepsins from the lysosomes to the cytosol was observed early in apoptosis. Cysteine cathepsins were found to be involved in activation of caspases in response to treatment with naphthazarin or anti-Fas antibodies, but inhibition of cysteine cathepsin activity was not sufficient to prevent cell death. Moreover, inhibition of cysteine cathepsin activity resulted in increased expression of the Fas death receptor, suggesting involvement of extracellular cysteine cathepsins in death receptor shedding.
Johansson
Ann-Charlotte
AC
Division of Pathology II, Faculty of Health Sciences, Linköping University, Linköping, Sweden. lotta.johansson@inr.liu.se
Norberg-Spaak
Lena
L
Roberg
Karin
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004151:Dipeptides / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007425:Intracellular Membranes / Q000276:immunology; D007659:Ketones / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D009062:Mouth Neoplasms / Q000473:pathology*; D015999:Multivariate Analysis; D009285:Naphthoquinones / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000276:immunology*
D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D007659:Ketones; D009285:Naphthoquinones; D019014:fas Receptor; C057383:MDL 201053; C005503:naphthazarin; D002403:Cathepsins; D020169:Caspases