Apoptosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-gamma through caspase 3 and caspase 8.
The cytotoxic effect of 5-FU has been shown by the induction of apoptosis in cancer cells, and reported to be enhanced by IFN-gamma. We examined the role of caspases on the apoptosis induction of 5-FU and IFN-gamma using a colorectal adenocarcinoma cell line. The activities of caspase 3 and caspase 8 increased when apoptosis was induced by 5-FU and/or IFN-gamma. Moreover, all apoptotic cells showed high caspase 3 activity in these conditions. Although the inhibitors of caspase 3 and caspase 8 inhibit apoptosis, anti-Fas ligand antibody does not affect the apoptosis induced by 5-FU. Thus, caspase 3 and caspase 8 play crucial roles in apoptosis induced by 5-FU and/or IFN-gamma, regardless of the Fas-Fas ligand system.
Adachi
Y
Y
First Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Taketani
S
S
Oyaizu
H
H
Ikebukuro
K
K
Tokunaga
R
R
Ikehara
S
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D011506:Proteins; C109664:caspase-activated DNase inhibitor; D019014:fas Receptor; D007371:Interferon-gamma; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D005472:Fluorouracil