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Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells
- Source :
- European journal of haematology. 75(3)
- Publication Year :
- 2005
-
Abstract
- Cyclooxygenase-2 (COX-2) is reported to be an important cellular target for therapy in malignancies. The growth inhibitory effects of COX-2 inhibitors on malignancies have been demonstrated to be through not only COX-2 dependent, but also independent mechanisms. In this study, we showed that etodolac, COX-2 inhibitor, induced apoptosis via COX-2 independent pathway, and investigated the molecular details of etodolac-induced apoptosis in Burkitt's lymphoma cells. In Daudi and Raji Burkitt's lymphoma cell lines, which expressed no COX-2 enzyme, etodolac more strongly induced apoptosis compared to meloxicam. Moreover, etodolac did not induce apoptosis to normal B-lymphocytes. For the pathway of etodolac-induced apoptosis, reduction of anti-apoptotic bcl-2 mRNA and Bcl-2 protein, activation of Caspase-9 and -3, down-regulation of caspase inhibitors, c-IAP-1 and Survivin were involved. Moreover, EBER-1 and -2 expression in Epstein–Barr virus positive Daudi and Raji cells were reduced to result in down-regulation of Bcl-2 by treatment with etodolac. It has been reported that etodolac has stereoisomers, R- and S-etodolac. We found that racemate of etodolac more strongly induced apoptosis in Daudi and Raji cells compared to R- or S-etodolac. In conclusion, our findings indicated etodolac inhibited EBERs expression and induced apoptosis via a Bcl-2-regulated pathway. Moreover, racemate of etodolac more effectively induced apoptosis than R- and/or S-etodolac. Therefore, these activities of etodolac potentially extend to the treatment of patients with Burkitt's lymphoma resistant to chemotherapy.
- Subjects :
- Blotting, Western
Thiazines
Apoptosis
Meloxicam
hemic and lymphatic diseases
Cell Line, Tumor
Survivin
medicine
Humans
Cyclooxygenase Inhibitors
RNA, Messenger
Etodolac
DNA Primers
Base Sequence
Cyclooxygenase 2 Inhibitors
Chemistry
Caspase 3
Reverse Transcriptase Polymerase Chain Reaction
Membrane Proteins
Hematology
General Medicine
Cell cycle
medicine.disease
Burkitt Lymphoma
Lymphoma
Raji cell
Gene Expression Regulation, Neoplastic
Thiazoles
Proto-Oncogene Proteins c-bcl-2
Cell culture
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Caspases
Cancer research
Cyclooxygenase 1
RNA, Viral
Burkitt's lymphoma
medicine.drug
Subjects
Details
- ISSN :
- 09024441
- Volume :
- 75
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- European journal of haematology
- Accession number :
- edsair.doi.dedup.....45f241d8004be02b803109ea2a184157