Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways

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	Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways
	Lu, Quanyi ; Lin, Xianghua ; Feng, Jean ; Zhao, Xiangmin ; Gallagher, Ruth ; Lee, Marietta Y. ; Chiao, Jen-Wei ; Liu, Delong ; Lu QY(鹿全意)
刊名	http://dx.doi.org/10.1186/1756-8722-1-6
	2008-06-09
关键词	SUBEROYLANILIDE HYDROXAMIC ACID HUMAN MULTIPLE-MYELOMA PROSTATE-CANCER CELLS MYELODYSPLASTIC SYNDROMES DEPSIPEPTIDE FR901228 PLASMA-CELLS P16 GENE IN-VIVO METHYLATION APOPTOSIS
英文摘要	New York Medical College Blood Diseases Fund.; Xiamen Zhongshan Hospital; Histone deacetylase (HDAC) inhibitors are a new class of chemotherapeutic agents. Our laboratory has recently reported that phenylhexyl isothiocyanate (PHI), a synthetic isothiocyanate, is an inhibitor of HDAC. In this study we examined whether PHI is a hypomethylating agent and its effects on myeloma cells. RPMI8226, a myeloma cell line, was treated with PHI. PHI inhibited the proliferation of the myeloma cells and induced apoptosis in a concentration as low as 0.5 mu M. Cell proliferation was reduced to 50% of control with PHI concentration of 0.5 mu M. Cell cycle analysis revealed that PHI caused GI-phase arrest of RPMI8226 cells. PHI induced p16 hypomethylation in a concentration-dependent manner. PHI was further shown to induce histone H3 hyperacetylation in a concentration-dependent manner. It was also demonstrated that PHI inhibited IL-6 receptor expression and VEGF production in the RPMI8226 cells, and reactivated p21 expression. It was found that PHI induced apoptosis through disruption of mitochondrial membrane potential. For the first time we show that PHI can induce both p16 hypomethylation and histone H3 hyperacetylation. We conclude that PHI has dual epigenetic effects on p16 hypomethylation and histone hyperacetylation in myeloma cells and targets several critical processes of myeloma proliferation.
语种	英语
出版者	J HEMATOL ONCOL
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93386]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Lu, Quanyi,Lin, Xianghua,Feng, Jean,et al. Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways[J]. http://dx.doi.org/10.1186/1756-8722-1-6,2008.
APA	Lu, Quanyi.,Lin, Xianghua.,Feng, Jean.,Zhao, Xiangmin.,Gallagher, Ruth.,...&鹿全意.(2008).Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways.http://dx.doi.org/10.1186/1756-8722-1-6.
MLA	Lu, Quanyi,et al."Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways".http://dx.doi.org/10.1186/1756-8722-1-6 (2008).