当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > 16-hydroxycleroda-3,13-dien-15,16-olide regulates the expression of histone-modifying enzymes PRC2 complex and induces apoptosis in CML K562 cells.

16-hydroxycleroda-3,13-dien-15,16-olide regulates the expression of histone-modifying enzymes PRC2 complex and induces apoptosis in CML K562 cells.

Abstract：

AIMS:Histone modifications play central epigenetic roles in regulating the entire genome of the cell and cell proliferation. Herein, we investigated the effects of the natural compound, 16-hydroxycleroda-3,13-dien-15,16-olide (PL3), on the expressions of histone-modifying enzymes, and examined how it induces apoptosis in leukemia K562 cells. MAIN METHODS:Cell proliferation was determined by an MTT assay, and histone-modifying enzyme gene expressions were investigated by a quantitative real-time PCR. Protein expressions were analyzed by a Western blot analysis. The histone H3K27 distribution was observed with immunofluorescence staining. To verify polycomb repressive complex 2 (PRC2) complex downstream gene expressions, a gene-expression array was performed to determine gene regulations. KEY FINDINGS:PL3 induced apoptosis and modulated many histone-modifying enzymes, especially the two PRC2 components, enhancer of zeste homolog 2 (EZH2) and suppressor of zeste 12 homolog (Suz12). Genes repressed by PRC2 were shown to be reactivated by PL3. Of these, 10 genes targeted by the PRC2 complex were identified, and expressions of 10 pro-/antiapoptotic genes were significantly regulated; these effects may have contributed to PL3-induced apoptosis in K562 cells. Regulation of other histone-modifying enzymes, including Aurora B, may also be involved in cell-cycle regulation. SIGNIFICANCE:Our data suggest that the induction of apoptosis by PL3 might partly occur through both a reduction in PRC2-mediated gene silencing and the reactivation of downstream tumor suppressor gene expressions. PL3 acts as a novel small-molecule histone modulator, which can potentially contribute to cancer chemotherapy singly or as a combined medication.

journal_name

Life Sci

journal_title

Life sciences

authors

Lin YH,Lee CC,Chang FR,Chang WH,Wu YC,Chang JG

doi

10.1016/j.lfs.2011.09.011

subject

Has Abstract

pub_date

2011-12-05 00:00:00

pages

886-95

issue

23-24

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(11)00453-X

journal_volume

89

pub_type

杂志文章

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