Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway

doi:10.1002/jcb.20173

	Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway
	Zhang, X ; Wei, L ; Yang, Y; Yu, Q
刊名	JOURNAL OF CELLULAR BIOCHEMISTRY
	2004-11-01
卷号	93 期号:4 页码:819-829
关键词	sodium 4-phenylbutyrate JNK apoptosis lung carcinoma RNA interference
ISSN号	0730-2312
DOI	10.1002/jcb.20173
文献子类	Article
英文摘要	Sodium 4-phenylbutyrate (PB) has been used in the therapy of urea cycle defects for many years. Recently, it has been shown to cause cellular differentiation, growth arrest, and apoptosis in certain malignancies. We have analyzed the effects of PB on human lung carcinoma cells. PB has distinct patterns of effects on different lung carcinoma cells, inducing apoptosis in NCl-H460 and NCl-H1792 cells, causing G1 arrest in A549 and SK-LU-1 cells, but having no effect on a non-transformed bronchial epithelial cell line HBE4-E6/E7. We investigated the role of MAP kinase family members, extracellular signal-regulated kinase (ERK), JNK, and p38 nitrogen-activated protein kinase (MAPK), as well as other important cell survival signaling molecules in PB-induced apoptosis. We observed activation of JNK and ERK by PB in the lung cancer cells. JNK was activated only in the two apoptotic cells, whereas ERK was activated in both the apoptotic and the growth-arrested cells, demonstrating a correlation between apoptosis and activation of JNK in response to PB. Both JNK inhibitor and JNK RNA interference (RNAi) inhibited PB-induced apoptosis, whereas MEK inhibitor did not, supporting that apoptosis induced by PB is through activation of JNK. De novo protein synthesis is required for the PB induced JNK activation and induction of apoptosis. However, the production of known upstream activators of JNK, namely Fas/Fas ligand, turner necrosis factor (TNF)-alpha, TNF-beta, and TRAIL, are not altered by PB treatment. Therefore, PB activates JNK through an unidentified and cell type-specific mechanism. Understanding of this mechanism is of therapeutic value in treating cancer patients with PB. (C) 2004 Wiley-Liss, lnc.
资助项目	NIGMS NIH HHS[R01 GM59678]
WOS关键词	BUTYRATE-INDUCED APOPTOSIS ; BREAST-CANCER CELLS ; KAPPA-B ACTIVATION ; MEDIATED APOPTOSIS ; PROTEIN-KINASES ; INHIBITION ; ARREST ; DEATH ; P38 ; DIFFERENTIATION
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	WILEY-LISS
WOS记录号	WOS:000224933200018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273999]
专题	中国科学院上海药物研究所
通讯作者	Yu, Q
作者单位	1.Boston Univ, Med Ctr, Dept Biochem, Boston, MA 02118 USA 2.Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Boston Univ, Med Ctr, Ctr Pulm, Dept Med, Boston, MA 02118 USA 4.Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510060, Peoples R China
推荐引用方式 GB/T 7714	Zhang, X,Wei, L,Yang, Y,et al. Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway[J]. JOURNAL OF CELLULAR BIOCHEMISTRY,2004,93(4):819-829.
APA	Zhang, X,Wei, L,Yang, Y,&Yu, Q.(2004).Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway.JOURNAL OF CELLULAR BIOCHEMISTRY,93(4),819-829.
MLA	Zhang, X,et al."Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway".JOURNAL OF CELLULAR BIOCHEMISTRY 93.4(2004):819-829.