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Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro‐apoptotic bax and inducing caspase‐3‐mediated cleavage of poly(ADP‐ribose) polymerase (PARP)
Author(s) -
Yinjun Lou,
Jie Jin,
Weilai Xu,
Xiangming Tong
Publication year - 2004
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20100
Subject(s) - poly adp ribose polymerase , homoharringtonine , apoptosis , downregulation and upregulation , chemistry , polymerase , cleavage (geology) , caspase 3 , microbiology and biotechnology , cancer research , biology , myeloid leukemia , programmed cell death , biochemistry , dna , gene , paleontology , fracture (geology)
Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL‐60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase‐3 activation, and cleavage of poly(ADP‐ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT‐induced cell death, whereas the expression of bcl‐2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia. Am. J. Hematol. 76:199–204, 2004. © 2004 Wiley‐Liss, Inc.