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Arsenic Trioxide Represses NF‐κB Activation and Increases Apoptosis in ATRA‐Treated APL Cells
Author(s) -
MATHIEU JULIE,
BESANÇON FRANÇOISE
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.022
Subject(s) - arsenic trioxide , acute promyelocytic leukemia , nf κb , chemistry , cancer research , apoptosis , retinoic acid , granulopoiesis , microbiology and biotechnology , biology , biochemistry , haematopoiesis , stem cell , gene
Acute promyelocytic leukemia (APL) is characterized by an arrest of granulopoiesis at the promyelocytic stage. The sensitivity of APL cells to all‐ trans retinoic acid (ATRA)‐induced differentiation has been successfully exploited for treatment of the disease. We previously reported that ATRA‐induced NF‐κB activation in APL cells is not essential for granulocytic differentiation, but prolongs the life span of mature cells. This prosurvival effect of NF‐κB results from its ability to repress c‐jun N terminal kinase (JNK) activation. We here report that arsenic trioxide (As 2 O 3 ) can overcome the antiapoptotic effect of ATRA‐induced NF‐κB activity. As 2 O 3 antagonizes ATRA‐induced degradation of the NF‐κB inhibitor IκB and consequently decreases NF‐κB activation. Also, cotreatment of NB4 cells with ATRA and As 2 O 3 results in a higher JNK activation than treatment with ATRA alone. Our results demonstrate a proapoptotic effect of As 2 O 3 in ATRA‐treated APL cells and suggest that As 2 O 3 may be helpful in reducing incidence of side effects linked to accumulation of mature cells, like the ATRA syndrome.