Triterpenoid CDDO-Im downregulates PML/RARα expression in acute promyelocytic leukemia cells

被引：17

作者：

Ikeda, T

Kimura, F

Nakata, Y

Sato, K

Ogura, K

Motoyoshi, K

Sporn, M

Kufe, D ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Natl Def Med Coll, Dept Internal Med 3, Saitama, Japan

[3] Dartmouth Coll, Sch Med, Dept Pharmacol, Hanover, NH 03755 USA

来源：

CELL DEATH AND DIFFERENTIATION | 2005年 / 12卷 / 05期

关键词：

PML/RAR alpha; PML; CDDO-Im; ATRA; ATO;

D O I：

10.1038/sj.cdd.4401574

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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/RAR alpha; (ii) enhancement of ATRA-induced differentiation; and (iii) sensitization of ATO-induced APL cell death.

引用

页码：523 / 531

页数：9

共 41 条

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