[Effect of trichostatin A on histone acetylation level and apoptosis in HL-60 cells].
In order to explore the underlying mechanism of high effects and low toxicity of trichostatin A (TSA), the effect of TSA on growth inhibition, histone acetylation level and apoptosis in HL-60 cells and normal human peripheral blood mononuclear cells (NPBMNC) were examined using MTT method, immunocytochemistry technology, and Annexin-V-FITC/PI double staining flow cytometry. The results showed that TSA inhibited growth of HL-60 in time- and dose-dependent manners, and the IC(50) of 36 hours was 100 ng/ml. The apoptosis induction effect of TSA in HL-60 cells was also time- and dose-dependent. Besides, the dose of TSA showing significant apoptotic cytotoxicity in HL-60 cells did not demonstrate apparent apoptosis induction in NPBMNC within definite dose and time range. The histone acetylation level in HL-60 cells and NPBMNC both showed remarkable increase (P < 0.05) after incubated with 100 ng/ml TSA for 4 hours without statistical difference between them is detected (P > 0.05). It is concluded that TSA shows effects of definite and significant growth inhibition and apoptosis induction on HL-60 cells in time- and dose-dependent manners. TSA is able to selectively induce apoptosis in HL-60 cells with low toxicity in NPBMNC at the same time. The mechanism of this selectivity can not be ascribed to the differential regulation of histone acetylation level between HL-60 cells and NPBMNC.
Chen
Wei-Kai
WK
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. chen-weikai@hotmail.com
Chen
Yan
Y
Gu
Jun-Xia
JX
Cui
Guo-Hui
GH
D000107:Acetylation; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D018922:HL-60 Cells / Q000187:drug effects; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D019098:Telomerase / Q000235:genetics
D004268:DNA-Binding Proteins; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D019098:Telomerase; D006655:Histone Deacetylases