Gene expression profiling for nitric oxide prodrug JS-K to kill HL-60 myeloid leukemia cells.
The nitric oxide (NO) prodrug JS-K is shown to have anticancer activity. To profile the molecular events associated with the anticancer effects of JS-K, HL-60 leukemia cells were treated with JS-K and subjected to microarray and real-time RT-PCR analysis. JS-K induced concentration- and time-dependent gene expression changes in HL-60 cells corresponding to the cytolethality effects. The apoptotic genes (caspases, Bax, and TNF-alpha) were induced, and differentiation-related genes (CD14, ITGAM, and VIM) were increased. For acute phase protein genes, some were increased (TP53, JUN) while others were suppressed (c-myc, cyclin E). The expression of anti-angiogenesis genes THBS1 and CD36 and genes involved in tumor cell migration such as tissue inhibitors of metalloproteinases, were also increased by JS-K. Confocal analysis confirmed key gene changes at the protein levels. Thus, multiple molecular events are associated with JS-K effects in killing HL-60, which could be molecular targets for this novel anticancer NO prodrug.
Liu
Jie
J
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Research Triangle Park, NC, USA. Liu6@niehs.nih.gov
Malavya
Swati
S
Wang
Xueqian
X
Saavedra
Joseph E
JE
Keefer
Larry K
LK
Tokar
Erik
E
Qu
Wei
W
Waalkes
Michael P
MP
Shami
Paul J
PJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology*; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009569:Nitric Oxide; D010879:Piperazines / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology; D015854:Up-Regulation
D000970:Antineoplastic Agents; D001391:Azo Compounds; D009363:Neoplasm Proteins; C474958:O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate; D010879:Piperazines; D011355:Prodrugs; D009569:Nitric Oxide