Homoharringtonine 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

Overview

Journal Cancer Med

Specialty Oncology

Date 2016 Oct 7

PMID 27709797

Citations 8

Authors

Jiang Cao

Hao Feng

Ning-Ning Ding

Qing-Yun Wu

Chong Chen

Ming-Shan Niu

Wei Chen

Ting-Ting Qiu

Hong-Hu Zhu

Kai-Lin Xu

Affiliations

Soon will be listed here.

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.

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