Abstract
5-Fluorouracil (5-FU) is frequently used in cancer treatment. Previous studies with 5-FU suggest that proapoptotic protein BAX and tumor suppressor protein TP53 are central factors in this process. As the leukemic T cell line Jurkat E6 has mutations in both these genes, we investigated a possible activation of alternative death pathways following 5-FU treatment. Here we show that 5-FU triggers apoptosis in Jurkat cells in a dose-dependent manner. Death responses were only moderately attenuated in the presence of a general caspase inhibitor. However, flow cytometric analysis showed activation of caspase 3 and a slight increase in ROS generation in a time- and dose-dependent manner. Furthermore, we observed 5-FU induced PARP cleavage and notably, reduced expression of antiapoptotic MCL-1L associated with the appearance of proapoptotic MCL-1S. Our results demonstrate the activation of alternative death pathways following treatment with 5-FU, despite mutations in the TP53 and BAX genes.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Chloromethyl Ketones / pharmacology
-
Antimetabolites, Antineoplastic / pharmacology*
-
Apoptosis / drug effects
-
Caspase 3 / metabolism*
-
Caspase Inhibitors
-
Cell Death / drug effects*
-
Cell Death / physiology
-
Cysteine Proteinase Inhibitors / pharmacology
-
Enzyme Activation / drug effects
-
Fluorouracil / pharmacology*
-
Humans
-
Jurkat Cells
-
Myeloid Cell Leukemia Sequence 1 Protein
-
Poly(ADP-ribose) Polymerases / metabolism
-
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
-
Proto-Oncogene Proteins c-bcl-2 / metabolism*
-
T-Lymphocytes / drug effects*
-
T-Lymphocytes / enzymology
-
T-Lymphocytes / metabolism*
-
T-Lymphocytes / pathology
Substances
-
Amino Acid Chloromethyl Ketones
-
Antimetabolites, Antineoplastic
-
Caspase Inhibitors
-
Cysteine Proteinase Inhibitors
-
Myeloid Cell Leukemia Sequence 1 Protein
-
Proto-Oncogene Proteins c-bcl-2
-
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
-
Poly(ADP-ribose) Polymerases
-
Caspase 3
-
Fluorouracil