| Summary: | 碩士 === 臺北醫學大學 === 醫學技術學系 === 93 === Abstract
Epigenetic control of gene expression plays an important role in hematopoiesis and leukemogenesis. One of the major components in epigenetic regulation of gene expression is histone acetylation.Recent studies have shown that histone deacetylase inhibitors (HDACIs) might be useful for treating hematopoietic malignancies. However the effects of these HDACIs on human acute myeloid leukemia (AML) have not been studied comprehensively. In this study, we examined the effects of several clinically available HDACIs on the proliferation, differentiation and apoptosis of AML in vitro. First HL-60 cells were treated with increasing concentrations of sodium butyrate (SB), a prototypic HDACI, phenylbutyrate (PB), and suberoylanilide hydroxamic acid (SAHA), an HDACI in phase-I clinical trials, valproic acid (VA) , a clinically available agent for neurological disorders.We found that SB, PB, and SAHA were able to arrest cell cycle at G0/G1 phase, but VA did not. SB and VA significantly induced the expression of CD11c and CD13, respectively. CD14 expression was upregulated by all four agents, All four agents induced mild neutrophilic and marked monocytic differentiation evidenced by nitroblue tetrazolium (NBT) tests andα-Naphthyl Acetate Esterase (NAE) staining,respectively. Further elucidation of VA induced apoptosis through both mitochondrial and death receptor pathway.VA induced cyclin D1, p21 and p27 expression, cycle D1 and p21 might relate cell differentiation,so cell cycle did not arrest at G0/G1 phase in 48H.Valproic acid activated JNK pathway might play an important role in monocytic differentiation.
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