Bufalin induces the apoptosis of acute promyelocytic leukemia cells via the downregulation of survivin expression.
OBJECTIVE
Bufalin is a cardiotonic steroid isolated from the Chinese toad venom preparation Chan'su and has been shown to induce leukemia cell differentiation and apoptosis under certain experimental conditions. However, the detailed mechanism by which bufalin induces the apoptosis of acute promyelocytic leukemia cells is largely unexplored.


METHODS
The acute promyelocytic leukemia cell line NB4 was treated with bufalin, then the proliferation was evaluated by cell viability assay and apoptosis was detected by flow cytometry analysis. In addition, NB4 cells were treated by MEK inhibitor PD98059 in combination with bufalin, and the expression of survivin and activation of caspase-3 were detected by Western blot analysis.


RESULTS
Bufalin inhibited the proliferation and induced the apoptosis of NB4 cells in a dose- and time-dependent manner. Moreover, bufalin synergized with PD98059 to inhibit the proliferation and induce the apoptosis of NB4 cells, which was associated with the downregulation of survivin expression and the upregulation of caspase-3 activation.


CONCLUSIONS
Bufalin is a potential regimen to be used in combination with conventional chemotherapeutic drugs to improve acute promyelocytic leukemia therapy.
Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, PR China. zhuzhitu@hotmail.com
Zhitu
Z
Zhu
Enze
E
Li
Yangyang
Y
Liu
Yu
Y
Gao
Hongzhi
H
Sun
Ying
Y
Wang
Zhenghua
Z
Wang
Xiaomei
X
Liu
Qingjun
Q
Wang
Yunpeng
Y
Liu
D017209:Apoptosis / Q000187:drug effects; D002018:Bufanolides / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D009360:Neoplastic Cells, Circulating; D000077022:Survivin
C107489:BIRC5 protein, human; D002018:Bufanolides; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D053148:Caspase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C022777:bufalin