Open AccessHomoharringtonine combined with aclarubicin and cytarabine synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase‐3‐mediated cleavage of the AML1‐ETO oncoprotein
Author(s) -
Cao Jiang,
Feng Hao,
Ding NingNing,
Wu Qingyun,
Chen Chong,
Niu MingShan,
Chen Wei,
Qiu TingTing,
Zhu HongHu,
Xu KaiLin
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.913
Subject(s) - homoharringtonine , aclarubicin , myeloid leukemia , cytarabine , apoptosis , leukemia , cancer research , cleavage (geology) , chemistry , biology , immunology , biochemistry , paleontology , fracture (geology)
Abstract Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO‐1 and Kasumi‐1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO‐1 and Kasumi‐1 cells. HAA caused cleavage of the AML1‐ETO (AE) oncoprotein to form truncated AE (ΔAE). Pretreatment with the caspase‐3 inhibitor caspase‐3 inhibitor Q‐DEVD‐OPh (QDO) not only suppressed HAA‐induced apoptosis but also abrogated the cleavage of AE and generation of ΔAE. These results suggest that HAA synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase‐3‐mediated cleavage of the AML1‐ETO oncoprotein, thus providing direct evidence for the strong activity of HAA toward t(8;21) AML.