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Triterpenoid CDDO-Im downregulates PML/RARĪ± expression in acute promyelocytic leukemia cells
- Source :
- Cell Death & Differentiation. 12:523-531
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) induces differentiation and apoptosis of diverse human tumor cells. In the present study, we examined the effects of the CDDO imidazolide imide (CDDO-Im) on the NB4 acute promyelocytic leukemia (APL) cell line and primary APL cells. The results show that CDDO-Im selectively downregulates expression of the PML/retinoic receptor alpha fusion protein by a caspase-dependent mechanism and sensitizes APL cells to the differentiating effects of all-trans retinoic acid (ATRA). CDDO-Im treatment of APL cells was also associated with disruption of redox balance and activation of the extrinsic apoptotic pathway. In concert with these results, CDDO-Im sensitizes APL cells to arsenic trioxide (ATO)-induced apoptosis. Our findings indicate that CDDO-Im may be effective in the treatment of APL by: (i) downregulation of PML/RARalpha; (ii) enhancement of ATRA-induced differentiation; and (iii) sensitization of ATO-induced APL cell death.
- Subjects :
- Acute promyelocytic leukemia
Programmed cell death
Receptors, Retinoic Acid
Recombinant Fusion Proteins
Retinoic acid
Down-Regulation
Apoptosis
Tretinoin
Promyelocytic Leukemia Protein
Arsenicals
Promyelocytic leukemia protein
chemistry.chemical_compound
Arsenic Trioxide
Leukemia, Promyelocytic, Acute
immune system diseases
Cell Line, Tumor
Tumor Cells, Cultured
medicine
Humans
Oleanolic Acid
Arsenic trioxide
neoplasms
Molecular Biology
biology
Gene Expression Regulation, Leukemic
Retinoic Acid Receptor alpha
Tumor Suppressor Proteins
Imidazoles
Nuclear Proteins
Oxides
Cell Biology
medicine.disease
Neoplasm Proteins
chemistry
Retinoic acid receptor alpha
Caspases
Immunology
biology.protein
Cancer research
Transcription Factors
medicine.drug
Subjects
Details
- ISSN :
- 14765403 and 13509047
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cell Death & Differentiation
- Accession number :
- edsair.doi.dedup.....7fd52ac4a4b498b78eeb7fcd15e49757