Enhancement of chemosensitivity toward anticancer drugs by high expression of caspase-1 in NIH 3T3 cells.
It has been well documented that caspase-1 (interleukin-1beta-converting enzyme, ICE) and its related cysteine proteinases such as caspase-3 (CPP32, apopain) and caspase-2 (ICH-1L) play important roles in apoptosis. In the present study, these genes were inserted into an inducible eukaryotic expression vector, pMSG, and transfected into NIH 3T3 mouse fibroblasts. The expression of caspases-1 and -3 was effectively induced by treatment with dexamethasone (Dex). The expression of caspase-2 was elevated in the transfected cells without treatment with Dex but was not further stimulated by Dex. High expression of these proteases alone induced neither apoptosis-like cell death nor any morphological change. However, the expression of caspase-1 but not of caspase-2 or -3 enhanced chemosensitivity toward cytotoxic anticancer drugs such as aclarubicin, epirubicin, adriamycin, nimustine and ifosfamide. It is thus concluded that caspase-1 mediates cytotoxic effects of these drugs.
Hiwasa
T
T
Department of Biochemistry, School of Medicine, Chiba University, Japan.
Tokita
H
H
Sakiyama
S
S
Nakagaware
A
A
D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone; D051379:Mice; D014162:Transfection
D000970:Antineoplastic Agents; D003907:Dexamethasone; D003546:Cysteine Endopeptidases; D020170:Caspase 1