[Mechanism of tetra-arsenic tetra-sulfide in inducing apoptosis of acute promyelocytic leukemia cells].
OBJECTIVE
To investigate the mechanism of tetra-arsenic tetra-sulfide (As4S4) in inducing apoptosis of acute promyelocytic leukemia (APL) cells.


METHODS
The gene expression patterns in NB4 cells pre- and post-treatment with As4S4 were analyzed by cDNA microarray, and differentially expressed genes related with apoptosis were identified. The mRNA expression levels of these apoptosis related genes in the peripheral blood of APL patients treated with As4S4 pre- and post-remission were examined by RT-PCR.


RESULTS
Among the differentially expressed genes in NB4 cells pre- and post-treatment with As4S4, two genes were related with cellular apoptosis, which were Apaf-1 and PNAS-2. Apaf1 ratio between pre- and post- As4S4 in NB4 cells was 2.910, PNAS-2 ratio was 0.420. RT-PCR results showed that the expression ratios of Apaf-1, caspase-9 and PNAS-2 in APL patients pre- and post-remission were 2.31 and 3.21, 0.99 respectively.


CONCLUSIONS
As4S4 induced cellular apoptosis in NB4 cells involves the expression changes of the two genes: the up-regulation of Apaf1 and down-regulation of PNAS-2. The increased expressions of Apaf1 and caspase-9 indicate that As4S4 induced apoptosis in APL cells is through mitochondrial pathway, but not the death-receptor pathway. The role played by PNAS-2 in cellular apoptosis needs to be clarified.
Teng
Zhi-ping
ZP
Institute of Hemotology, Peking University People's Hospital, Beijing 100044, China. tengzhipiong@sina.com
Zhang
Ping
P
Zhu
Hong-hu
HH
Hao
Hong-ying
HY
Qin
Xiao-ying
XY
Hao
Le
L
Xu
Hong
H
Lu
Dao-pei
DP
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics*; D001151:Arsenic / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*; D056827:Endosomal Sorting Complexes Required for Transport
D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D001151:Arsenic; D001152:Arsenicals; D012333:RNA, Messenger; D013440:Sulfides; C499838:CHMP5 protein, human; D056827:Endosomal Sorting Complexes Required for Transport