Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells.
Selenium at a low concentration has a chemopreventive role against cancer, while at a high concentration, it exerts a direct antitumor effect. However, the mechanisms remain elusive. In this article, we discovered that Na(2)SeO(3) at 20 micromol/l concentration could significantly inhibit the proliferation of NB4 cells, affect the cell cycle distribution of cell population, and induce cellular changes characteristic of apoptotic cells, while this same compound at 2 micromol/l concentration had no such effects. The mechanisms underlying these overt differences caused by treatment of different concentrations of selenium were further investigated. cDNA microarray analysis showed that after treatment by 20 micromol/l Na(2)SeO(3), 34 genes were changed in expression, while treatment by 2 micromol/l Na(2)SeO(3) resulted in the changes of 29 genes. Nine genes were regulated in both groups, among which three showed opposite changes caused by 2 and 20 micromol/l Na(2)SeO(3). The majority of regulated genes did not coincide between the two experiment groups. In conclusion, 2 and 20 micromol/l Na(2)SeO(3) could have different effects on NB4 cells, and some genes might be involved in the underlying mechanisms. Our findings could provide basis for further uncovering the molecular mechanisms of the chemopreventive and antitumor effects of selenium and, in turn, for probing the rationality of treating leukemia with selenium.
Cao
Ting-Ming
TM
National Laboratory of Medical Molecular Biology, Institute of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, People's Republic of China.
Hua
Fang-Yuan
FY
Xu
Cai-Min
CM
Han
Bing-She
BS
Dong
Hua
H
Zuo
Lu
L
Wang
Xuan
X
Yang
Yang
Y
Pan
Hua-Zhen
HZ
Zhang
Zhi-Nan
ZN
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018038:Sodium Selenite / Q000494:pharmacology*
D017931:DNA Primers; D018038:Sodium Selenite