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- Title
Triterpenoid CDDO-Im downregulates PML/RARα expression in acute promyelocytic leukemia cells.
- Authors
Ikeda, T.; Kimura, F; Nakata, Y.; Sato, K.; Ogura, K.; Motoyoshi, K.; Sporn, M.; Kufe, D.
- 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/RARα; (ii) enhancement of ATRA-induced differentiation; and (iii) sensitization of ATO-induced APL cell death.Cell Death and Differentiation (2005) 12, 523–531. doi:10.1038/sj.cdd.4401574 Published online 4 March 2005
- Subjects
PRELEUKEMIA; CELLS; LEUCOCYTOSIS; APOPTOSIS; CELL death; CANCER
- Publication
Cell Death & Differentiation, 2005, Vol 12, Issue 5, p523
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4401574