Mortalization of human promyelocytic leukemia HL-60 cells to be more susceptible to sodium butyrate-induced apoptosis and inhibition of telomerase activity by down-regulation of nucleophosmin/B23.
Vanadate (10 microM), a potent inhibitor of tyrosine phosphatase, added simultaneously potentiated BuONa-induced (1 mM) apoptosis. The steady-state level of nucleophosmin/B23 mRNA and the total cellular nucleophosmin/B23 protein decreased during the BuONa/vanadate-induced apoptosis. Stabilization and promotor transcriptional activity assays indicate that the decrease in nucleophosmin/B23 mRNA in BuONa/vanadate-treated HL-60 cells was transcriptionally regulated. A decline in telomerase activity was observed in HL-60 cells treated with BuONa/vanadate for 24-96 h. There was virtually no decline of nucleophosmin/B23 mRNA nor the telomerase activities during the growth arrest by serum-starvation. The decrease in nucleophosmin/B23 mRNA expression and telomerase activity in HL-60 cells subsequent to BuONa/vanadate treatment can thus be attributed to cellular apoptosis rather than the growth arrest induced by BuONa/vanadate. Nucleophosmin/B23 antisense oligomer treatment significantly potentiated BuONa-induced apoptosis and inhibition of telomerase activity. Results of this study suggest that nucleophosmin/B23 is one of the key elements in the down-regulation of nucleolar function for cellular apoptosis and mortalization.
Liu
W H
WH
Department of Pharmacology, College of Medicine, Chang Gung University, Taiwan, Republic of China.
Yung
B Y
BY
D017209:Apoptosis; D002087:Butyrates / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic; D014638:Vanadates / Q000494:pharmacology
D002087:Butyrates; D004791:Enzyme Inhibitors; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000090243:Nucleophosmin; D014638:Vanadates; D019098:Telomerase